Evaluation of a deformable image registration quality assurance tool for head and neck cancer patients.

INTRODUCTION: A challenge in implementing deformable image registration (DIR) in radiation therapy planning is effectively communicating registration accuracy to the radiation oncologist. This study aimed to evaluate the MIM® quality assurance (QA) tool for rating DIR accuracy. METHODS: Retrospective DIR was performed on CT images for 35 head and neck cancer patients. The QA tool was used to rate DIR accuracy as good, fair or bad. Thirty registered patient images were assessed independently by three RTs and a further five patients assessed by five RTs. Ratings were evaluated by comparison of Hausdorff Distance (HD), Mean Distance to Agreement (MDA), Dice Similarity Coefficients (DSC) and Jacobian determinants for parotid and mandible subregions on the two CTs post-DIR. Inter-operator reliability was assessed using Krippendorff's alpha coefficient (KALPA). Rating time and volume measures for each rating were also calculated. RESULTS: Quantitative metrics calculated for most anatomical subregions reflected the expected trend by registration accuracy, with good obtaining the most ideal values on average (HD = 7.50 ± 3.18, MDA = 0.64 ± 0.47, DSC = 0.90 ± 0.07, Jacobian = 0.95 ± 0.06). Highest inter-operator reliability was observed for good ratings and within the parotids (KALPA 0.66-0.93), whilst ratings varied the most in regions of dental artefact. Overall, average rating time was 33 minutes and the least commonly applied rating by volume was fair. CONCLUSION: Results from qualitative and quantitative data, operator rating differences and rating time suggest highlighting only bad regions of DIR accuracy and implementing clinical guidelines and RT training for consistent and efficient use of the QA tool.

Pulmonary Hypertension in Central Australia: A Community-Based Cohort Study.

BACKGROUND: The burden of pulmonary hypertension (PHT) in Central Australia has not been previously studied. Our aim is to characterise the prevalence, clinical classification, and long-term survival of individuals with PHT in Central Australia. METHODS: A community-based cohort study of all individuals diagnosed with PHT in Central Australia between 2005 and 2016 was undertaken. We estimated PHT prevalence using population data, describe clinical PHT classification, and characterised long-term survival using Kaplan-Meier approaches. RESULTS: A total of 183 patients were identified (mean age 52±16years, 63% female). Of these individuals, 149 (81.4%) were of Aboriginal and Torres Strait Islander (ATSI) descent. The prevalence per 100,000 of any PHT was significantly higher In ATSI (723 [95% CI 608-839] compared to non-ATSI individuals (126 [95% CI 84-168], p<0.001). Furthermore, ATSI individuals were diagnosed at younger ages compared to non-ATSI individuals (49±15 vs 64±16years, p<0.001). Median estimated pulmonary artery systolic pressure (ePASP) was higher in patients with pulmonary arterial hypertension (PAH) compared to other causes (62 [IQR 54-69] vs 50 [IQR 44-58] mmHg, p<0.01). The median survival rate from diagnosis was 9 years (IQR 7.2-13.2). Age and ePASP were significant predictors of mortality (HR 1.05 [95% CI 1.02-1.07] and HR 1.56 [95% 1.00-2.42] respectively). CONCLUSIONS: In this community based study, we found a high burden of PHT in Central Australia. The prevalence of PHT is greater in ATSI individuals and is diagnosed at younger ages compared to non-ATSI individuals. Together with other cardiovascular diseases, PHT may be in-part contributing to the gap in life expectancy between ATSI and non-ATSI individuals.

Oral colonization by Streptococcus mutans and caries development is reduced upon deletion of carbonic anhydrase VI expression in saliva.

Carbonic anhydrase VI (CA VI), encoded by type A transcripts of the gene Car6, is a secretory product of salivary glands and is found in the enamel pellicle. Because higher caries prevalence is associated with lower salivary concentrations of CA VI in humans, we tested whether CA VI protects enamel surfaces from caries induced by Streptococcus mutans, using Car6(-/-) mice, in which salivary CA VI expression is absent. We detected aberrant Car6 type A transcripts in Car6(-/-) mice, likely targets for nonsense-mediated mRNA decay. Expression of the intracellular stress-induced isoform of CA VI encoded by type B transcripts was restricted to parotid and submandibular glands of wild type mice. The salivary function of Car6(-/-) mice was normal as assessed by the histology and protein/glycoprotein profiles of glands, salivary flow rates and protein/glycoprotein compositions of saliva. Surprisingly, total smooth surface caries and sulcal caries in Car6(-/-) mice were more than 6-fold and 2-fold lower than in wild type mice after infection with S. mutans strain UA159. Recoveries of S. mutans and total microbiota from molars were also lower in Car6(-/-) mice. To explore possible mechanisms for increased caries susceptibility, we found no differences in S. mutans adherence to salivary pellicles, in vitro. Interestingly, higher levels of Lactobacillus murinus and an unidentified Streptococcus species were cultivated from the oral microbiota of Car6(-/-) mice. Collective results suggest salivary CA VI may promote caries by modulating the oral microbiota to favor S. mutans colonization and/or by the enzymatic production of acid within plaque.