Imaging Performance of Quantitative Transmission Ultrasound

Quantitative Transmission Ultrasound (QTUS) is a tomographic transmission ultrasound modality that is capable of generating 3D speed-of-sound maps of objects in the field of view. It performs this measurement by propagating a plane wave through the medium from a transmitter on one side of a water tank to a high resolution receiver on the opposite side. This information is then used via inverse scattering to compute a speed map. In addition, the presence of reflection transducers allows the creation of a high resolution, spatially compounded reflection map that is natively coregistered to the speed map. A prototype QTUS system was evaluated for measurement and geometric accuracy as well as for the ability to correctly determine speed of sound

Computed tomography assessment of peripubertal craniofacial morphology in a sheep model of binge alcohol drinking in the first trimester

Identification of facial dysmorphology is essential for the diagnosis of fetal alcohol syndrome (FAS); however, most children with fetal alcohol spectrum disorders (FASD) do not meet the dysmorphology criterion. Additional objective indicators are needed to help identify the broader spectrum of children affected by prenatal alcohol exposure. Computed tomography (CT) was used in a sheep model of prenatal binge alcohol exposure to test the hypothesis that quantitative measures of craniofacial bone volumes and linear distances could identify alcohol-exposed lambs. Pregnant sheep were randomly assigned to four groups: heavy binge alcohol, 2.5 g/kg/day (HBA); binge alcohol, 1.75 g/kg/day (BA); saline control (SC); and normal control (NC). Intravenous alcohol (BA; HBA) or saline (SC) infusions were given three consecutive days per week from gestation day 4-41, and a CT scan was performed on postnatal day 182. The volumes of eight skull bones, cranial circumference, and 19 linear measures of the face and skull were compared among treatment groups. Lambs from both alcohol groups showed significant reduction in seven of the eight skull bones and total skull bone volume, as well as cranial circumference. Alcohol exposure also decreased four of the 19 craniofacial measures. Discriminant analysis showed that alcohol-exposed and control lambs could be classified with high accuracy based on total skull bone volume, frontal, parietal, or mandibular bone volumes, cranial circumference, or interorbital distance. Total skull volume was significantly more sensitive than cranial circumference in identifying the alcohol-exposed lambs when alcohol-exposed lambs were classified using the typical FAS diagnostic cutoff of ≤10th percentile. This first demonstration of the usefulness of CT-derived craniofacial measures in a sheep model of FASD following binge-like alcohol exposure during the first trimester suggests that volumetric measurement of cranial bones may be a novel biomarker for binge alcohol exposure during the first trimester to help identify non-dysmorphic children with FASD

Maternal choline supplementation in a sheep model of first trimester binge alcohol fails to protect against brain volume reductions in peripubertal lambs

Fetal alcohol spectrum disorder (FASD) is a leading potentially preventable birth defect. Poor nutrition may contribute to adverse developmental outcomes of prenatal alcohol exposure, and supplementation of essential micronutrients such as choline has shown benefit in rodent models. The sheep model of first-trimester binge alcohol exposure was used in this study to model the dose of maternal choline supplementation used in an ongoing prospective clinical trial involving pregnancies at risk for FASD. Primary outcome measures included volumetrics of the whole brain, cerebellum, and pituitary derived from magnetic resonance imaging (MRI) in 6-month-old lambs, testing the hypothesis that alcohol-exposed lambs would have brain volume reductions that would be ameliorated by maternal choline supplementation. Pregnant sheep were randomly assigned to one of five groups – heavy binge alcohol (HBA; 2.5 g/kg/treatment ethanol), heavy binge alcohol plus choline supplementation (HBC; 2.5 g/kg/treatment ethanol and 10 mg/kg/day choline), saline control (SC), saline control plus choline supplementation (SCC; 10 mg/kg/day choline), and normal control (NC). Ewes were given intravenous alcohol (HBA, HBC; mean peak BACs of ~280 mg/dL) or saline (SC, SCC) on three consecutive days per week from gestation day (GD) 4–41; choline was administered on GD 4–148. MRI scans of lamb brains were performed postnatally on day 182. Lambs from both alcohol groups (with or without choline) showed significant reductions in total brain volume; cerebellar and pituitary volumes were not significantly affected. This is the first report of MRI-derived volumetric brain reductions in a sheep model of FASD following binge-like alcohol exposure during the first trimester. These results also indicate that maternal choline supplementation comparable to doses in human studies fails to prevent brain volume reductions typically induced by first-trimester binge alcohol exposure. Future analyses will assess behavioral outcomes along with regional brain and neurohistological measures

Emission computed tomography for guidance of sampling and therapeutic delivery

Treatment for a variety of diseases often requires guidance for the delivery of either a drug or radiation to the disease site. Positron Emission Tomography (PET) can provide three dimensional positioning of the location of positron emitting radioisotopes that can mark a disease site. However, the inversion of the raw emission projection data into a 3D volume is computationally intensive, and this results in a low update or frame rate. In order to be useful in either guiding a surgeon, or some other automated feedback approach, the update/frame rate must be of sufficient speed that the user can effectively control the process. This approach provides a substantial improvement to the frame rate by taking advantage of iterative reconstruction methodologies to shortcut the reconstruction process.U

Emission computed tomography for guidance of sampling and therapeutic delivery

Treatment for a variety of diseases often requires guidance for the delivery of either a drug or radiation to the disease site. Positron Emission Tomography (PET) can provide three dimensional positioning of the location of positron emitting radioisotopes that can mark a disease site. However, the inversion of the raw emission projection data into a 3D volume is computationally intensive, and this results in a low update or frame rate. In order to be useful in either guiding a surgeon, or some other automated feedback approach, the update/frame rate must be of sufficient speed that the user can effectively control the process. This approach provides a substantial improvement to the frame rate by taking advantage of iterative reconstruction methodologies to shortcut the reconstruction process.U

Emission computed tomography for guidance of sampling and therapeutic delivery

Treatment for a variety of diseases often requires guidance for the delivery of either a drug or radiation to the disease site. Positron Emission Tomography (PET) can provide three dimensional positioning of the location of positron emitting radioisotopes that can mark a disease site. However, the inversion of the raw emission projection data into a 3D volume is computationally intensive, and this results in a low update or frame rate. In order to be useful in either guiding a surgeon, or some other automated feedback approach, the update/frame rate must be of sufficient speed that the user can effectively control the process. This approach provides a substantial improvement to the frame rate by taking advantage of iterative reconstruction methodologies to shortcut the reconstruction process.U

Emission computed tomography for guidance of sampling and therapeutic delivery

Treatment for a variety of diseases often requires guidance for the delivery of either a drug or radiation to the disease site. Positron Emission Tomography (PET) can provide three dimensional positioning of the location of positron emitting radioisotopes that can mark a disease site. However, the inversion of the raw emission projection data into a 3D volume is computationally intensive, and this results in a low update or frame rate. In order to be useful in either guiding a surgeon, or some other automated feedback approach, the update/frame rate must be of sufficient speed that the user can effectively control the process. This approach provides a substantial improvement to the frame rate by taking advantage of iterative reconstruction methodologies to shortcut the reconstruction process.U

Resource utilisation, costs and clinical outcomes in non-institutionalised patients with Alzheimer’s disease: 18-month UK results from the GERAS observational study

Abstract Background Alzheimer’s disease (AD), the commonest cause of dementia, represents a significant cost to UK society. This analysis describes resource utilisation, costs and clinical outcomes in non-institutionalised patients with AD in the UK. Methods The GERAS prospective observational study assessed societal costs associated with AD for patients and caregivers over 18 months, stratified according to baseline disease severity (mild, moderate, or moderately severe/severe [MS/S]). All patients enrolled had an informal caregiver willing to participate in the study. Healthcare resource utilisation was measured using the Resource Utilization in Dementia instrument, and 18-month costs estimated by applying unit costs of services and products (2010 values). Total societal costs were calculated using an opportunity cost approach. Results Overall, 526 patients (200 mild, 180 moderate and 146 MS/S at baseline) were recruited from 24 UK centres. Mini-Mental State Examination (MMSE) scores deteriorated most markedly in the MS/S patient group, with declines of 3.6 points in the mild group, 3.5 points in the moderate group and 4.7 points in the MS/S group; between-group differences did not reach statistical significance. Patients with MS/S AD dementia at baseline were more likely to be institutionalised (Kaplan–Meier probability 28% versus 9% in patients with mild AD dementia; p < 0.001 for difference across all severities) and had a greater probability of death (Kaplan–Meier probability 15% versus 5%; p = 0.013) at 18 months. Greater disease severity at baseline was also associated with concomitant increases in caregiver time and mean total societal costs. Total societal costs of £43,560 over 18 months were estimated for the MS/S group, versus £25,865 for the mild group and £30,905 for the moderate group (p < 0.001). Of these costs, over 50% were related to informal caregiver costs at each AD dementia severity level. Conclusions This study demonstrated a mean deterioration in MMSE score over 18 months in patients with AD. It also showed that AD is a costly disease, with costs increasing with disease severity, even when managed in the community: informal caregiver costs represented the main contributor to societal costs

Potential cost savings to be made by slowing cognitive decline in mild Alzheimer’s disease dementia using a model derived from the UK GERAS observational study

Abstract Background Given the high costs associated with the care of those with Alzheimer’s disease (AD) dementia, we examined the likely impact of a reduction in the rate of cognitive decline upon cost outcomes associated with this disease. Methods Using the group of patients with mild AD dementia from the GERAS study, generalised linear modelling (GLM) was used to explore the relationship between change in cognition as measured using the Mini-Mental State Examination (MMSE) and UK overall costs (health care and social care costs, and total societal costs) associated with AD dementia. Results A total of 200 patients with mild AD dementia were identified. Least squares mean (LSM) ± standard error (SE) reduction in MMSE score was 3.6 ± 0.4 points over 18 months. Using GLM it was possible to calculate that this worsening in cognition was associated with an 8.7% increase in total societal costs, equating to an increase of approximately £2200 per patient over an 18-month period. If the rate of decline in cognition was reduced by 30% or 50%, the associated savings in total societal costs over 18 months would be approximately £670 and £1100, respectively, of which only £110 and £180, respectively, could be attributed to a saving of health care costs. Conclusion This study demonstrates that there are potential savings to be made in the care of patients with AD dementia through reducing the rate of cognitive decline. A reduction in wider societal costs is likely to be the main contributor to these potential savings, and need to be further evaluated when intervention costs and cost offsets can be measured

Imaging Performance of Quantitative Transmission Ultrasound

Quantitative Transmission Ultrasound (QTUS) is a tomographic transmission ultrasound modality that is capable of generating 3D speed-of-sound maps of objects in the field of view. It performs this measurement by propagating a plane wave through the medium from a transmitter on one side of a water tank to a high resolution receiver on the opposite side. This information is then used via inverse scattering to compute a speed map. In addition, the presence of reflection transducers allows the creation of a high resolution, spatially compounded reflection map that is natively coregistered to the speed map. A prototype QTUS system was evaluated for measurement and geometric accuracy as well as for the ability to correctly determine speed of sound