Single-centre experience with peptide receptor radionuclide therapy for neuroendocrine tumours (NETs): results using a theranostic molecular imaging-guided approach.

AIM: To summarise our centre's experience managing patients with neuroendocrine tumours (NETs) in the first 5 years after the introduction of peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-octreotate (LUTATE). The report emphasises aspects of the patient management related to functional imaging and use of radionuclide therapy. METHODS: We describe the criteria for treatment with LUTATE at our centre, the methodology for patient selection, and the results of an audit of clinical measures, imaging results and patient-reported outcomes. Subjects are treated initially with four cycles of ~ 8 GBq of LUTATE administered as an outpatient every 8 weeks. RESULTS: In the first 5 years offering LUTATE, we treated 143 individuals with a variety of NETs of which approx. 70% were gastroentero-pancreatic in origin (small bowel: 42%, pancreas: 28%). Males and females were equally represented. Mean age at first treatment with LUTATE was 61 ± 13 years with range 28-87 years. The radiation dose to the organs considered most at risk, the kidneys, averaged 10.6 ± 4.0 Gy in total. Median overall survival (OS) from first receiving LUTATE was 72.5 months with a median progression-free survival (PFS) of 32.3 months. No evidence of renal toxicity was seen. The major long-term complication seen was myelodysplastic syndrome (MDS) with a 5% incidence. CONCLUSIONS: LUTATE treatment for NETs is a safe and effective treatment. Our approach relies heavily on functional and morphological imaging informing the multidisciplinary team of NET specialists to guide appropriate therapy, which we suggest has contributed to the favourable outcomes seen.

Partial volume effect in SPECT & PET imaging and impact on radionuclide dosimetry estimates.

Objectives: The spatial resolution of emission tomographic imaging systems can lead to a significant underestimation in the apparent radioactivity concentration in objects of size comparable to the resolution volume of the system. The aim of this study was to investigate the impact of the partial volume effect (PVE) on clinical imaging in PET and SPECT with current state-of-the-art instrumentation and the implications that this has for radionuclide dosimetry estimates. Methods: Using the IEC Image Quality Phantom we have measured the underestimation in observed uptake in objects of various sizes for both PET and SPECT imaging conditions. Both single pixel measures (i.e., SUVmax) and region of interest mean values were examined over a range of object sizes. We have further examined the impact of the PVE on dosimetry estimates in OLINDA in 177Lu SPECT imaging based on a subject with multiple somatostatin receptor positive paragangliomas in the head and neck. Results: In PET, single pixel estimates of uptake are affected for objects less than approximately 18 mm in minor axis with existing systems. In SPECT imaging with medium energy collimators (e.g., for 177Lu imaging), however, the underestimates are far greater, where single pixel estimates in objects less than 2-3×the resolution volume are significantly impacted. In SPECT, region of interest mean values are underestimated in objects less than 10 cm in diameter. In the clinical case example, the dosimetry measured with SPECT ranged from more than 60% underestimate in the largest lesion (28×22 mm in maximal cross-section; 10.2 cc volume) to >99% underestimate in the smallest lesion (4×5 mm; 0.06 cc). Conclusion: The partial volume effect remains a significant factor when estimating radionuclide uptake in vivo, especially in small volumes. Accurate estimates of absorbed dose from radionuclide therapy will be particularly challenging until robust solutions to correct for the PVE are found.

Practical learning through radiation physics problem solving.

INTRODUCTION: The identification of unknown radionuclides is an authentic practical activity for students that provides the foundations for clinical problem solving, especially in the storage and management of radioactive waste. As different radionuclides have different half-lives, some of which are quite long, the storage of waste material has to accommodate the longest of these. Cross contamination requires a method of identifying the radionuclide samples in a mixed sample to safely and appropriately manage disposal. Similarly, identifying a single unknown sample of a radionuclide allows correct handling and disposal. METHODS: Performing a systematic investigation of the physical properties of unknown radioactive samples is a rich learning opportunity to instil understanding of important physics principles among students in nuclear medicine. RESULTS: This manuscript outlines an investigation developed that would allow students to identify single unknown radionuclides based on physical properties and identify the constituent radionuclides of a mixed sample using some additional mathematical curve stripping. CONCLUSION: The processes and solutions are provided with real data and this practical activity can be replicated by students generating their own data. IMPLICATIONS FOR PRACTICE: This paper provides a template and analysis/interpretation guideline for educators and clinicians to deepen understanding of foundation physics. Enhanced and deeper understanding are a vehicle for improved problem solving in clinical and research practice.

Theranostic SPECT reconstruction for improved resolution: application to radionuclide therapy dosimetry.

BACKGROUND: SPECT-derived dose estimates in tissues of diameter less than 3× system resolution are subject to significant losses due to the limited spatial resolution of the gamma camera. Incorporating resolution modelling (RM) into the SPECT reconstruction has been proposed as a possible solution; however, the images produced are prone to noise amplification and Gibbs artefacts. We propose a novel approach to SPECT reconstruction in a theranostic setting, which we term SPECTRE (single photon emission computed theranostic reconstruction); using a diagnostic PET image, with its superior resolution, to guide the SPECT reconstruction of the therapeutic equivalent. This report demonstrates a proof in principle of this approach. METHODS: We have employed the hybrid kernelised expectation maximisation (HKEM) algorithm implemented in STIR, with the aim of producing SPECT images with PET-equivalent resolution. We demonstrate its application in both a dual 68Ga/177Lu IEC phantom study and a clinical example using 64Cu/67Cu. RESULTS: SPECTRE is shown to produce images comparable in accuracy and recovery to PET with minimal introduction of artefacts and amplification of noise. CONCLUSION: The SPECTRE approach to image reconstruction shows improved quantitative accuracy with a reduction in noise amplification. SPECTRE shows great promise as a method of improving SPECT radioactivity concentrations, directly leading to more accurate dosimetry estimates in small structures and target lesions. Further investigation and optimisation of the algorithm parameters is needed before this reconstruction method can be utilised in a clinical setting.

Obesity alters the topographical distribution of ventilation and the regional response to bronchoconstriction.

Obesity is associated with reduced operating lung volumes that may contribute to increased airway closure during tidal breathing and abnormalities in ventilation distribution. We investigated the effect of obesity on the topographical distribution of ventilation before and after methacholine-induced bronchoconstriction using single-photon emission computed tomography (SPECT)-computed tomography (CT) in healthy subjects. Subjects with obesity (n = 9) and subjects without obesity (n = 10) underwent baseline and postbronchoprovocation SPECT-CT imaging, in which Technegas was inhaled upright and followed by supine scanning. Lung regions that were nonventilated (Ventnon), low ventilated (Ventlow), or well ventilated (Ventwell) were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. To determine regional ventilation, lungs were divided into upper, middle, and lower thirds of axial length, derived from CT. At baseline, Ventnon and Ventlow for the entire lung were similar in subjects with and without obesity. However, in the upper lung zone, Ventnon (17.5 ± 10.6% vs. 34.7 ± 7.8%, P < 0.001) and Ventlow (25.7 ± 6.3% vs. 33.6 ± 5.1%, P < 0.05) were decreased in subjects with obesity, with a consequent increase in Ventwell (56.8 ± 9.2% vs. 31.7 ± 10.1%, P < 0.001). The greater diversion of ventilation to the upper zone was correlated with body mass index (rs = 0.74, P < 0.001), respiratory system resistance (rs = 0.72, P < 0.001), and respiratory system reactance (rs = -0.64, P = 0.003) but not with lung volumes or basal airway closure. Following bronchoprovocation, overall Ventnon increased similarly in both groups; however, in subjects without obesity, Ventnon only increased in the lower zone, whereas in subjects with obesity, Ventnon increased more evenly across all lung zones. In conclusion, obesity is associated with altered ventilation distribution during baseline and following bronchoprovocation, independent of reduced lung volumes.NEW & NOTEWORTHY Using ventilation SPECT-computed tomography imaging in healthy subjects, we demonstrate that ventilation in obesity is diverted to the upper lung zone and that this is strongly correlated with body mass index but is independent of operating lung volumes and of airway closure. Furthermore, methacholine-induced bronchoconstriction only occurred in the lower lung zone in individuals who were not obese, whereas in subjects who were obese, it occurred more evenly across all lung zones. These findings show that obesity-associated factors alter the topographical distribution of ventilation.

Combined PET/MRI: Global Warming-Summary Report of the 6th International Workshop on PET/MRI, March 27-29, 2017, Tübingen, Germany.

The 6th annual meeting to address key issues in positron emission tomography (PET)/magnetic resonance imaging (MRI) was held again in Tübingen, Germany, from March 27 to 29, 2017. Over three days of invited plenary lectures, round table discussions and dialogue board deliberations, participants critically assessed the current state of PET/MRI, both clinically and as a research tool, and attempted to chart future directions. The meeting addressed the use of PET/MRI and workflows in oncology, neurosciences, infection, inflammation and chronic pain syndromes, as well as deeper discussions about how best to characterise the tumour microenvironment, optimise the complementary information available from PET and MRI, and how advanced data mining and bioinformatics, as well as information from liquid biomarkers (circulating tumour cells and nucleic acids) and pathology, can be integrated to give a more complete characterisation of disease phenotype. Some issues that have dominated previous meetings, such as the accuracy of MR-based attenuation correction (AC) of the PET scan, were finally put to rest as having been adequately addressed for the majority of clinical situations. Likewise, the ability to standardise PET systems for use in multicentre trials was confirmed, thus removing a perceived barrier to larger clinical imaging trials. The meeting openly questioned whether PET/MRI should, in all cases, be used as a whole-body imaging modality or whether in many circumstances it would best be employed to give an in-depth study of previously identified disease in a single organ or region. The meeting concluded that there is still much work to be done in the integration of data from different fields and in developing a common language for all stakeholders involved. In addition, the participants advocated joint training and education for individuals who engage in routine PET/MRI. It was agreed that PET/MRI can enhance our understanding of normal and disrupted biology, and we are in a position to describe the in vivo nature of disease processes, metabolism, evolution of cancer and the monitoring of response to pharmacological interventions and therapies. As such, PET/MRI is a key to advancing medicine and patient care.

Combined PET/MRI: from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tübingen, Germany.

This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tübingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.

Diagnosis of upper limb lymphedema: development of an evidence-based approach.

BACKGROUND: The diagnosis of secondary upper limb lymphedema (LE) is complicated by the lack of an agreed-upon measurement tool and diagnostic threshold. The aim of this study was to determine which of the many commonly used and normatively determined clinical diagnostic thresholds has the best diagnostic accuracy of secondary upper limb LE, when compared to diagnosis by an appropriate reference standard, lymphoscintigraphy. MATERIAL AND METHODS: The arms of women treated for breast cancer with and without a previous diagnosis of LE, as well as healthy controls, were assessed using lymphoscintigraphy, bioimpedance spectroscopy (BIS) and perometry. Dermal backflow score determined from lymphoscintigraphy imaging assessment (reference standard) was compared with diagnosis by both commonly used and normatively determined diagnostic thresholds for volume and circumference measurements as well as BIS. RESULTS: For those with established dermal backflow, all commonly used and normatively determined diagnostic thresholds accurately identified presence of LE compared with lymphoscintigraphy diagnosis. In participants with mild to moderate changes in dermal backflow, only a normatively determined diagnostic threshold, set at two standard deviations above the norm, for arm circumference and full arm BIS were found to have both high sensitivity (81% and 76%, respectively) and specificity (96% and 93%, respectively). For this group, strong, and clinically useful, positive (23 and 10, respectively) and negative likelihood (0.2 and 0.3) ratios were found for both the circumference and bioimpedance diagnostic thresholds. CONCLUSION: For the first time, evidence-based clinical diagnostic thresholds have been established for secondary LE. With mild LE, normatively determined circumference and BIS thresholds are superior to the commonly used thresholds.

Periodontal diagnosis in private dental practice: a case-based survey.

BACKGROUND: Despite the prevalence of periodontitis in Australia, there are few reports regarding periodontal diagnosis and therapies in the general dental practice setting. This study aimed to assess the degree of diagnostic accuracy in periodontal cases of Victorian general dental practitioners. METHODS: Following ethics approval, dentists were invited to complete a scenario-based questionnaire on the Australian Dental Association Victorian Branch (ADAVB) website. Five text-based clinical scenarios (from a total of 10) were randomly presented, representing patients with a range of disease levels from periodontal health/gingivitis to severe periodontitis, and respondents were asked what examinations they would usually perform. Based upon the presented results of periodontal and radiographic examinations, a periodontal diagnosis was requested. RESULTS: One hundred and thirty-five dentists attempted the survey. Most were in group practice and based in Melbourne; 22.5% of respondents worked in a practice employing a hygienist. The clinical parameters most commonly measured to diagnose periodontal disease were pocket depth and mobility. The majority of respondents diagnosed health, gingivitis and mild periodontitis correctly compared to American Academy of Periodontology guidelines. However, moderate periodontitis tended to be diagnosed as severe. CONCLUSIONS: Dentists in Victoria used appropriate clinical parameters when assessing periodontal disease and were generally accurate in their diagnoses. There is a need for consensus regarding diagnostic definitions.

Combined PET/MRI: Multi-modality Multi-parametric Imaging Is Here: Summary Report of the 4th International Workshop on PET/MR Imaging; February 23-27, 2015, Tübingen, Germany.

This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both technical versatility and acceptance by clinical and research-driven users from the status quo of last year. Still, with only minimal evidence of progress made in exploiting the true complementary nature of the PET and MRI-based information, PET/MRI is still yet to achieve its potential. In that regard, the conclusion of last year's meeting "the real work has just started" still holds true.

Combined PET/MR: The Real Work Has Just Started. Summary Report of the Third International Workshop on PET/MR Imaging; February 17-21, 2014, Tübingen, Germany.

This paper summarises the proceedings and discussions at the third annual workshop held in Tübingen, Germany, dedicated to the advancement of the technical, scientific and clinical applications of combined PET/MRI systems in humans. Two days of basic scientific and technical instructions with "hands-on" tutorials were followed by 3 days of invited presentations from active researchers in this and associated fields augmented by round-table discussions and dialogue boards with specific themes. These included the use of PET/MRI in paediatric oncology and in adult neurology, oncology and cardiology, the development of multi-parametric analyses, and efforts to standardise PET/MRI examinations to allow pooling of data for evaluating the technology. A poll taken on the final day demonstrated that over 50 % of those present felt that while PET/MRI technology underwent an inevitable slump after its much-anticipated initial launch, it was now entering a period of slow, progressive development, with new key applications emerging. In particular, researchers are focusing on exploiting the complementary nature of the physiological (PET) and biochemical (MRI/MRS) data within the morphological framework (MRI) that these devices can provide. Much of the discussion was summed up on the final day when one speaker commented on the state of PET/MRI: "the real work has just started".

Trends of oral health care and dental treatment needs in relation to molar incisor hypomineralisation defects: a study amongst a group of Iraqi schoolchildren.

BACKGROUND: The dynamic properties of molar-incisor-hypomineralisation lesions (MIH) may impact negatively on personal daily oral care resulting in increased treatment needs. AIMS: To describe and compare individual oral health care practices between MIH-affected and non-affected children, to evaluate and compare dental treatment needs between hypomineralised and non-hypomineralised first permanent molars, and to explore the role of reported fluoride exposure in the development of MIH. STUDY DESIGN: A cluster sample of 7-9 year-old Iraqi schoolchildren (823 of 1000 eligible, response rate 82.3%) had their first permanent molars and incisors evaluated using the European Academy of Paediatric Dentistry evaluation criteria for MIH. Of these 153 were diagnosed with the defect and were referred to as MIH-affected children. METHODS: Mothers of the participating children were asked to complete an oral health-questionnaire administered at schools. This included questions regarding child's history of dental visits, fluoride intake and the pattern of oral hygiene practices. Assessment of the dental treatment requirements for the first permanent molars was performed in a sample subset drawn from a larger data set of affected children (n=100) having their teeth assessed previously for dental caries status following the International Caries Detection and Assessment System. The sample subset consisted of 130 hypomineralised molars and 270 non-hypomineralised molars. RESULTS: Of the total sample, approximately 71% of parents had taken their children to the dentist at some stage. For the total sample, tooth restoration or extraction was the most likely causes for seeking dental care at the first dental appointment (57.9%). Tap water was the main source of water consumed at home by the majority of children (77.8%). The prevalence of dental caries and tooth restorations was higher in hypomineralised affected molars (78.5%) than in the defect-free molars (33.7%). STATISTICS: MIH-affected children reported significantly higher frequency of seeking dental care than their non-affected counterparts (82.4%, 68.2%; respectively). They were over three times (OR = 3.18) more likely to visit the dentist complaining of pain and were over six times (OR = 6.37) more likely to seek dental care due to tooth sensitivity than their non-affected peers. No significant differences were found between the study groups in terms of tooth brushing and toothpaste history with brushing frequency "once-a-day" was commonly reported in both groups (75.5%). Early exposure to fluoridated water appeared to have a protective effect for MIH (OR=0.38). Affected molars required more than twice the amount of restorative care than unaffected molars. CONCLUSIONS: MIH did not seem to have an impact on the personal daily oral hygiene practices; however, MIH patients were commonly seeking dental consultation and needed care more often to improve their oral health.

Risk factors of hypomineralised second primary molars in a group of Iraqi schoolchildren.

AIM: To investigate risk factor/s involved in the development of hypomineralised second primary molars and to relate the location of the affected tooth in the dental arches with the timing of the illness/condition incidence. STUDY DESIGN: A cluster sample of 1,000, Iraqi 7-9 year-old children were invited to have their second primary molars examined for demarcated hypomineralised lesions. METHODS: Mothers of 823 children completed a questionnaire-based interview regarding pregnancy and childhood systemic health history. In the clinical examination, the buccal, occlusal and lingual/palatal surfaces of the second primary molar were evaluated for demarcated hypomineralisation lesions by visual examination. RESULTS: A response rate of 82.3% was obtained. Of the children examined, 53 (6.6%) had hypomineralisation defects in at least one second primary molar and were considered as the hypomineralised second primary molar-affected group. Of the total affected teeth (n=83), maxillary molars were the teeth most frequently affected by hypomineralisation throughout all developmental stages (69.9%). Demarcated opacities were the most prevalent lesion type (71.0%). Ninety-four percent of subjects diagnosed with demarcated defects reported various medical conditions possibly associated with hypomineralisation compared with 44% for their non-affected counterparts. Peri-natal medical conditions (45.3%) were the most frequently reported followed by pre-natal and post-natal conditions (24.5%, 9.4%; respectively). STATISTICS: Ill health during pregnancy, delivery complications, neonatal complications, acute childhood illness, birth weight and duration of breast feeding were significant potential risk factors (p<0.05). The greater the number of health events reported, the higher was the chance of developing the defect. Children who experienced neonatal complications and whose mothers reported pregnancy and birth problems were approximately six times more likely to have the defect than those whose mothers had delivery complications only (80% vs 14.6%) (p<0.001). Also of those children whose mothers did not report delivery complications, but were breastfed for less than six months, of low birth weight and had history of upper respiratory tract infection, the chance of hypomineralised defects was over four times more likely to happen than in those who did not suffer any of these problems (25.8% vs 6.7%) (p<0.01). No statistically significant association was revealed between the time of the illness/condition occurrence and the location of the tooth in the dental arches. CONCLUSIONS: Children with hypomineralised second primary molars had experienced more medical conditions than their unaffected peers particularly during the peri-natal period. No single factor was identified as a potential cause, leaving the aetiology of the defect unclear.

Using an external gating signal to estimate noise in PET with an emphasis on tracer avid tumors.

The purpose of this study is to establish and validate a methodology for estimating the standard deviation of voxels with large activity concentrations within a PET image using replicate imaging that is immediately available for use in the clinic. To do this, ensembles of voxels in the averaged replicate images were compared to the corresponding ensembles in images derived from summed sinograms. In addition, the replicate imaging noise estimate was compared to a noise estimate based on an ensemble of voxels within a region. To make this comparison two phantoms were used. The first phantom was a seven-chamber phantom constructed of 1 liter plastic bottles. Each chamber of this phantom was filled with a different activity concentration relative to the lowest activity concentration with ratios of 1:1, 1:1, 2:1, 2:1, 4:1, 8:1 and 16:1. The second phantom was a GE Well-Counter phantom. These phantoms were imaged and reconstructed on a GE DSTE PET/CT scanner with 2D and 3D reprojection filtered backprojection (FBP), and with 2D- and 3D-ordered subset expectation maximization (OSEM). A series of tests were applied to the resulting images that showed that the region and replicate imaging methods for estimating standard deviation were equivalent for backprojection reconstructions. Furthermore, the noise properties of the FBP algorithms allowed scaling the replicate estimates of the standard deviation by a factor of 1/square root N, where N is the number of replicate images, to obtain the standard deviation of the full data image. This was not the case for OSEM image reconstruction. Due to nonlinearity of the OSEM algorithm, the noise is shown to be both position and activity concentration dependent in such a way that no simple scaling factor can be used to extrapolate noise as a function of counts. The use of the Well-Counter phantom contributed to the development of a heuristic extrapolation of the noise as a function of radius in FBP. In addition, the signal-to-noise ratio for high uptake objects was confirmed to be higher with backprojection image reconstruction methods. These techniques were applied to several patient data sets acquired in either 2D or 3D mode, with (18)F (FLT and FDG). Images of the standard deviation and signal-to-noise ratios were constructed and the standard deviations of the tumors' uptake were determined. Finally, a radial noise extrapolation relationship deduced in this paper was applied to patient data.

The impact of changing dental needs on cost savings from fluoridation.

BACKGROUND: Although community water fluoridation has been one of the cornerstone strategies for the prevention and control of dental caries, questions are still raised regarding its cost-effectiveness. This study assessed the impact of changing dental needs on the cost savings from community water fluoridation in Australia. METHODS: Net costs were estimated as Costs((programme)) minus Costs((averted caries).) Averted costs were estimated as the product of caries increment in non-fluoridated community, effectiveness of fluoridation and the cost of a carious surface. Modelling considered four age-cohorts: 6-20, 21-45, 46-65 and 66+ years and three time points 1970s, 1980s, and 1990s. Cost of a carious surface was estimated by conventional and complex methods. Real discount rates (4, 7 (base) and 10%) were utilized. RESULTS: With base-case assumptions, the average annual cost savings/person, using Australian dollars at the 2005 level, ranged from $56.41 (1970s) to $17.75 (1990s) (conventional method) and from $249.45 (1970s) to $69.86 (1990s) (complex method). Under worst-case assumptions fluoridation remained cost-effective with cost savings ranging from $24.15 (1970s) to $3.87 (1990s) (conventional method) and $107.85 (1970s) and $24.53 (1990s) (complex method). For 66+ years cohort (1990s) fluoridation did not show a cost saving, but costs/person were marginal. CONCLUSIONS: Community water fluoridation remains a cost-effective preventive measure in Australia.

Regression of post-orthodontic lesions by a remineralizing cream.

Orthodontic patients have an increased risk of white-spot lesion formation. A clinical trial was conducted to test whether, in a post-orthodontic population using fluoride toothpastes and receiving supervised fluoride mouthrinses, more lesions would regress in participants using a remineralizing cream containing casein phosphopeptide- amorphous calcium phosphate compared with a placebo. Forty-five participants (aged 12-18 yrs) with 408 white-spot lesions were recruited, with 23 participants randomized to the remineralizing cream and 22 to the placebo. Product was applied twice daily after fluoride toothpaste use for 12 weeks. Clinical assessments were performed according to ICDAS II criteria. Transitions between examinations were coded as progressing, regressing, or stable. Ninety-two percent of lesions were assessed as code 2 or 3. For these lesions, 31% more had regressed with the remineralizing cream than with the placebo (OR = 2.3, P = 0.04) at 12 weeks. Significantly more post-orthodontic white-spot lesions regressed with the remineralizing cream compared with a placebo over 12 weeks.

Consumption of milk with added casein phosphopeptide-amorphous calcium phosphate remineralizes enamel subsurface lesions in situ.

BACKGROUND: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is an anticariogenic agent that is suitable to be added to foods. The aim of this double-blind, three-way crossover randomized study was to investigate the capacity of CPP-ACP, when added to bovine milk, to remineralize enamel subsurface lesions in situ. METHODS: Ten subjects drank 100 mL of bovine milk containing no added CPP-ACP (control milk), 0.2% (w/v) CPP-ACP or 0.3% (w/v) CPP-ACP, for 30 seconds once daily for 15 days, whilst wearing removable appliances with attached slabs of enamel containing subsurface enamel lesions. After each treatment and a one-week washout period, subjects crossed over to another treatment and this was repeated until they had consumed each of the three milk products. At the completion of each treatment the enamel slabs were removed and remineralization was determined using microradiography. RESULTS: The results demonstrated that all three milk samples remineralized enamel subsurface lesions in situ. However, the two milk samples containing added CPP-ACP each produced significantly greater remineralization than the control milk. CONCLUSIONS: The remineralizing effect of CPP-ACP in milk was dose-dependent with milk containing 0.2% CPP-ACP and 0.3% CPP-ACP producing an increase in mineral content of 81% and 164%, respectively, relative to the control milk.

The anticariogenic effect of sugar-free gum containing CPP-ACP nanocomplexes on approximal caries determined using digital bitewing radiography.

This study investigated, using digital bitewing radiography, the progression and regression of approximal caries in adolescent subjects chewing a sugar-free gum containing 54 mg CPP-ACP relative to the identical gum without CPP-ACP. 2,720 subjects from 29 schools were randomly assigned to one of the two gums and were instructed to chew their assigned gum for 3 x 10 min/day, with one session supervised on school days, over the 24-month study period. Standardized digital bitewing radiographs were taken at the baseline and 24-month clinical examinations for each subject. The radiographs, scored by a single examiner, were assessed for approximal surface dental caries at both the enamel and dentine level. Surface level transitions were scored using a transition matrix. Caries progression or regression was analysed using proportional-odds ordered logistic regression modelling of the transition scores at the tooth surface level. There was a statistically significant difference in the frequency distributions of the transition scores between the two gum groups (OR = 0.82, p = 0.03). For subjects chewing the CPP-ACP gum the odds of a surface experiencing caries progression were 18% less than those of a surface experiencing caries progression for subjects chewing the control gum. In conclusion, the 54 mg CPP-ACP sugar-free gum significantly slowed progression and enhanced regression of approximal caries relative to a control sugar-free gum in a 24-month clinical trial.

Rigid-body transformation of list-mode projection data for respiratory motion correction in cardiac PET.

High-resolution cardiac PET imaging with emphasis on quantification would benefit from eliminating the problem of respiratory movement during data acquisition. Respiratory gating on the basis of list-mode data has been employed previously as one approach to reduce motion effects. However, it results in poor count statistics with degradation of image quality. This work reports on the implementation of a technique to correct for respiratory motion in the area of the heart at no extra cost for count statistics and with the potential to maintain ECG gating, based on rigid-body transformations on list-mode data event-by-event. A motion-corrected data set is obtained by assigning, after pre-correction for detector efficiency and photon attenuation, individual lines-of-response to new detector pairs with consideration of respiratory motion. Parameters of respiratory motion are obtained from a series of gated image sets by means of image registration. Respiration is recorded simultaneously with the list-mode data using an inductive respiration monitor with an elasticized belt at chest level. The accuracy of the technique was assessed with point-source data showing a good correlation between measured and true transformations. The technique was applied on phantom data with simulated respiratory motion, showing successful recovery of tracer distribution and contrast on the motion-corrected images, and on patient data with C15O and 18FDG. Quantitative assessment of preliminary C15O patient data showed improvement in the recovery coefficient at the centre of the left ventricle.