Assessment of the Prognostic Value of Radiomic Features in 18F-FMISO PET Imaging of Hypoxia in Postsurgery Brain Cancer Patients: Secondary Analysis of Imaging Data from a Single-Center Study and the Multicenter ACRIN 6684 Trial.

Hypoxia is associated with resistance to radiotherapy and chemotherapy in malignant gliomas, and it can be imaged by positron emission tomography with 18F-fluoromisonidazole (18F-FMISO). Previous results for patients with brain cancer imaged with 18F-FMISO at a single center before conventional chemoradiotherapy showed that tumor uptake via T/Bmax (tissue SUVmax/blood SUV) and hypoxic volume (HV) was associated with poor survival. However, in a multicenter clinical trial (ACRIN 6684), traditional uptake parameters were not found to be prognostically significant, but tumor SUVpeak did predict survival at 1 year. The present analysis considered both study cohorts to reconcile key differences and examine the potential utility of adding radiomic features as prognostic variables for outcome prediction on the combined cohort of 72 patients with brain cancer (30 University of Washington and 42 ACRIN 6684). We used both 18F-FMISO intensity metrics (T/Bmax, HV, SUV, SUVmax, SUVpeak) and assessed radiomic measures that determined first-order (histogram), second-order, and higher-order radiomic features of 18F-FMISO uptake distributions. A multivariate model was developed that included age, HV, and the intensity of 18F-FMISO uptake. HV and SUVpeak were both independent predictors of outcome for the combined data set (P < .001) and were also found significant in multivariate prognostic models (P < .002 and P < .001, respectively). Further model selection that included radiomic features showed the additional prognostic value for overall survival of specific higher order texture features, leading to an increase in relative risk prediction performance by a further 5%, when added to the multivariate clinical model..

TB or not TB? That is the question regarding TB treatment in a remote provincial hospital in Solomon Islands.

INTRODUCTION: Tuberculosis (TB) remains a significant public health challenge in Solomon Islands. Limited healthcare resources, geography, and sociocultural beliefs, coupled with lack of laboratory diagnostic tools, leads to diagnostic and treatment outcome uncertainty. METHODS: Kirakira Hospital (KKH) is the main provincial hospital of Makira-Ulawa Province in Solomon Islands. A retrospective clinical audit of hospitalised TB patients in KKH over a 2-year period between July 2015 and July 2017 was conducted. The cost of TB treatment was estimated by calculating the total number of inpatient bed days of treatment. RESULTS: Data were available for 42 of 78 listed TB patients including 23 males and 19 females, and 9 children aged less than 16 years. The average age was 35 years (range 9 months - 74 years). Thirty-five of these received a chest X-ray. All patients had at least one of the following: fever, night sweats, chronic cough and haemoptysis as part of their clinical TB presentation. Thirty-six completed the full 8-week duration of intensive HRZE treatment as inpatients of KKH. The audit shows the treatment of TB consumes 15% of the current healthcare budget of Makira-Ulawa Province. CONCLUSION: TB remains a common clinical diagnosis in KKH. TB consumes 15% of the current healthcare budget of Makira-Ulawa Province. The limited capacity and data about the management of TB in Makira province mean that it is not currently possible to measure if there has been any progress towards eradicating TB in Solomon Islands. Laboratory investigations for TB available in Makira including sputum analysis and the GeneXpert are required to improve the accuracy of diagnosis and identify multidrug resistant strains of TB. This needs to be coupled with robust monitoring and data collection of both inpatients and outpatients to ensure the current treatment protocols for TB are being followed in Makira-Ulawa Province. These steps are essential if TB is to be eradicated from the provinces of Solomon Islands by 2030.

ACRIN 6684: Multicenter, phase II assessment of tumor hypoxia in newly diagnosed glioblastoma using magnetic resonance spectroscopy.

A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) "A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)", was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials.

High perinatal mortality rates persist in Kirakira: The sustainable development goals for health remain out of reach in the provinces of Solomon Islands.

AIM: This study aimed to calculate the perinatal mortality rate in Kirakira Hospital, a remote provincial hospital in Solomon Islands, over a 3-year period, from 2014 to 2016. METHODS: A retrospective audit of the labour ward admission books for the years 2014-2016 was conducted. Patient files of all perinatal deaths and caesarean sections were accessed and reviewed. Stillbirths and early neonatal deaths were classified, and results were compared with the national health statistics of Australia (2014). RESULTS: Between 2014 and 2016, there were 1311 births and 40 perinatal deaths (mortality rate of 31 per 1000). This is approximately three times the Australian rate of 9.6 deaths per 1000. Of these deaths, 28 were stillbirths, and 12 were neonatal deaths. Detailed information was available for 88% (35/40) of the perinatal deaths. Only 15 caesarean sections (1.1% of deliveries) were performed, compared to a rate of 32.1% of caesarean sections in Australia (2014). CONCLUSIONS: Kirakira continues to have a very high perinatal mortality rate that has not changed over the last 6 years. The rate is double that reported for Solomon Islands in current World Health Organization data. This discrepancy is likely due to an absence of clinical data outside of the National Referral Hospital in Honiara. This paper identifies clinical indicators that could be targeted to help lower the perinatal mortality rate in this remote and impoverished community.

ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI.

PURPOSE: Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma. EXPERIMENTAL DESIGN: Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (ktrans) as well as 18F-Fluoromisonidazole (18F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival. RESULTS: Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment 18F-FMISO SUVpeak (P = 0.048), mean ktrans (P = 0.024), and median ktrans (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median ktrans (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUVpeak [AUC = 0.75; 95% confidence interval (CI), 0.59-0.91], nRCBV (AUC = 0.72; 95% CI, 0.56-0.89), and nCBF (AUC = 0.72; 95% CI, 0.56-0.89) were predictive of survival at 1 year. CONCLUSIONS: Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and 18F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. ©2016 AACR.

Scintigraphic assessment of radio-aerosol pulmonary deposition with the acapella positive expiratory pressure device and various nebulizer configurations.

BACKGROUND: The Acapella device produces high-frequency oscillations and positive expiratory pressure to promote bronchial secretion clearance. Its performance during aerosol delivery has not been described. We evaluated the effect of nebulizer and Acapella configuration on pulmonary deposition of radio-tagged aerosol in healthy subjects. METHODS: Ten healthy male subjects (mean age 24.4 ± 2.2 y) participated in a crossover study that compared pulmonary delivery of 4 mL of technetium-99m-labeled diethylene triamine penta-acetic acid (25 mCi) and 0.9% saline solution via jet nebulizer. We tested 3 configurations: nebulizer attached to the distal end of the Acapella; nebulizer placed between the mouthpiece and the Acapella; and nebulizer alone (control). With scintigraphy we measured radio-aerosol deposition in 6 lung regions: upper, middle, lower, central, intermediate, and peripheral. RESULTS: Deposition was similar between the right and left lungs, with no significant differences between device configurations. Lung deposition was less with the nebulizer attached to the Acapella than with nebulizer between the mouthpiece and the Acapella (P = .001, for both lungs) or without the Acapella (P = .003 and P = .001 for the right and left lungs, respectively). There was no significant difference between the setup without Acapella and the setup with the nebulizer between the mouthpiece and the Acapella (P = .001, for both lungs). On the vertical axis, deposition was lower with the nebulizer attached to the distal end of the Acapella than with the nebulizer between the mouthpiece and the Acapella (upper region P < .001, middle region P = .001, lower region P = .003), and lower with the nebulizer attached to the distal end of the Acapella than with the setup without Acapella (upper and middle region both P = .001, lower region P = .002), with up to a 3-fold difference in the middle and lower regions. On the central-peripheral axis, deposition was lower with the nebulizer attached to the distal end of the Acapella than with the nebulizer between the mouthpiece and the Acapella (central region P < .001, peripheral region P < .001), and lower with the nebulizer attached to the distal end of the Acapella than with the setup without Acapella (central and peripheral regions both P = .002), with differences of 3-4-fold between the central and peripheral regions. CONCLUSIONS: Placing the nebulizer distal to the Acapella, as recommended by the manufacturer, decreased intrapulmonary deposition, compared to placing the nebulizer between the Acapella and the patient airway, or delivering aerosol without the Acapella in the circuit. (ClinicalTrials.gov NCT01102166).

Imaging of cerebellopontine angle masses: self-assessment module.

The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the imaging features of cerebellopontine angle (CPA) masses and the role of advanced MRI in the differential diagnosis of CPA masses.

Sonographic NASCET index: a new doppler parameter for assessment of internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Established Doppler parameters for carotid stenosis assessment do not reflect North American Symptomatic Carotid Endarterectomy Trial (NASCET)-style methodology. We derived a Doppler parameter, termed sonographic NASCET index (SNI), and hypothesized that the SNI would provide greater angiographic correlation and better accuracy in predicting stenosis of 70% or greater than that of currently used peak systolic velocity (PSV) measurements. METHODS: Inclusion criteria of angiographically proved carotid stenoses of 40-95% and measured proximal and distal internal carotid artery Doppler PSV values were established. Occlusions and near occlusions were specifically excluded. Doppler and angiographic data meeting the inclusion criteria from 32 carotid bifurcations were identified; actual angiographic stenoses ranged 40-89%. SNI values were calculated for each vessel. PSV and SNI were correlated with angiography by using linear regression analysis. Accuracies of SNI and PSV in predicting stenosis of 70% or greater were compared at two thresholds. RESULTS: Correlation between SNI and angiography was superior to that between PSV and angiography (r2=0.64 vs 0.38). PSV and SNI values that corresponded to 70% angiographic stenosis were 345 cm/s and 45.5, respectively. Accuracy of PSV of 345 cm/s or greater in predicting stenosis of 70% or greater was 78%, compared with 88% for SNI of 45.5 or greater. The SNI value that corresponded to a PSV threshold of 250 cm/s was 33. Accuracy of PSV of 250 cm/s or greater in predicting stenosis of 70% or greater was 81%, compared with 88% for SNI of 33 or greater. CONCLUSION: Correlation between SNI and angiography was greater than that between PSV and angiography. Accuracy of SNI in predicting stenosis of 70% or greater was also superior to that of PSV at two thresholds. These results suggest that SNI may be a better predictor of high-grade carotid stenosis than is PSV.