Advanced quantitative evaluation of PET systems using the ACR phantom and NiftyPET software.

PURPOSE: A novel phantom-imaging platform, a set of software tools, for automated and high-precision imaging of the American College of Radiology (ACR) positron emission tomography (PET) phantom for PET/magnetic resonance (PET/MR) and PET/computed tomography (PET/CT) systems is proposed. METHODS: The key feature of this platform is the vector graphics design that facilitates the automated measurement of the knife-edge response function and hence image resolution, using composite volume of interest templates in a 0.5 mm resolution grid applied to all inserts of the phantom. Furthermore, the proposed platform enables the generation of an accurate µ $\mu$ -map for PET/MR systems with a robust alignment based on two-stage image registration using specifically designed PET templates. The proposed platform is based on the open-source NiftyPET software package used to generate multiple list-mode data bootstrap realizations and image reconstructions to determine the precision of the two-stage registration and any image-derived statistics. For all the analyses, iterative image reconstruction was employed with and without modeled shift-invariant point spread function and with varying iterations of the ordered subsets expectation maximization (OSEM) algorithm. The impact of the activity outside the field of view (FOV) was assessed using two acquisitions of 30 min each, with and without the activity outside the FOV. RESULTS: The utility of the platform has been demonstrated by providing a standard and an advanced phantom analysis including the estimation of spatial resolution using all cylindrical inserts. In the imaging planes close to the edge of the axial FOV, we observed deterioration in the quantitative accuracy, reduced resolution (FWHM increased by 1-2 mm), reduced contrast, and background uniformity due to the activity outside the FOV. Although it slows convergence, the PSF reconstruction had a positive impact on resolution and contrast recovery, but the degree of improvement depended on the regions. The uncertainty analysis based on bootstrap resampling of raw PET data indicated high precision of the two-stage registration. CONCLUSIONS: We demonstrated that phantom imaging using the proposed methodology with the metric of spatial resolution and multiple bootstrap realizations may be helpful in more accurate evaluation of PET systems as well as in facilitating fine tuning for optimal imaging parameters in PET/MR and PET/CT clinical research studies.

A semi-empirical model for scatter field reduction in digital mammography.

X-ray mammography is the gold standard technique in breast cancer screening programmes. One of the main challenges that mammography is still facing is scattered radiation, which degrades the quality of the image and complicates the diagnosis process. Anti-scatter grids, the main standard physical scattering reduction technique, have some unresolved challenges as they increase the dose delivered to the patient, do not remove all the scattered radiation and increase the cost of the equipment. Alternative scattering reduction methods based on post-processing algorithms, have lately been under investigation. This study is concerned with the use of image post-processing to reduce the scatter contribution in the image, by convolving the primary plus scatter image with kernels obtained from simplified Monte Carlo (MC) simulations. The proposed semi-empirical approach uses up to five thickness-dependant symmetric kernels to accurately estimate the scatter contribution of different areas of the image. Single breast thickness-dependant kernels can over-estimate the scatter signal up to 60%, while kernels adapting to local variations have to be modified for each specific case adding high computational costs. The proposed method reduces the uncertainty to a 4%-10% range for a 35-70 mm breast thickness range, making it a very efficient, case-independent scatter modelling technique. To test the robustness of the method, the scattered corrected image has been successfully compared against full MC simulations for a range of breast thicknesses. In addition, clinical images of the 010A CIRS phantom were acquired with a mammography system with and without the presence of the anti-scatter grid. The grid-less images were post-processed and their quality was compared against the grid images, by evaluating the contrast-to-noise ratio and variance ratio using several test objects, which simulate calcifications and tumour masses. The results obtained show that the method reduces the scatter to similar levels than the anti-scatter grids.

Correction to: Practical issues and limitations of brain attenuation correction on a simultaneous PET-MR scanner.

An amendment to this paper has been published and can be accessed via the original article.

Practical issues and limitations of brain attenuation correction on a simultaneous PET-MR scanner.

BACKGROUND: Despite the advent of clinical PET-MR imaging for routine use in 2011 and the development of several methods to address the problem of attenuation correction, some challenges remain. We have identified and investigated several issues that might affect the reliability and accuracy of current attenuation correction methods when these are implemented for clinical and research studies of the brain. These are (1) the accuracy of converting CT Hounsfield units, obtained from an independently acquired CT scan, to 511 keV linear attenuation coefficients; (2) the effect of padding used in the MR head coil; (3) the presence of close-packed hair; (4) the effect of headphones. For each of these, we have examined the effect on reconstructed PET images and evaluated practical mitigating measures. RESULTS: Our major findings were (1) for both Siemens and GE PET-MR systems, CT data from either a Siemens or a GE PET-CT scanner may be used, provided the conversion to 511 keV µ-map is performed by the PET-MR vendor's own method, as implemented on their PET-CT scanner; (2) the effect of the head coil pads is minimal; (3) the effect of dense hair in the field of view is marked (> 10% error in reconstructed PET images); and (4) using headphones and not including them in the attenuation map causes significant errors in reconstructed PET images, but the risk of scanning without them may be acceptable following sound level measurements. CONCLUSIONS: It is important that the limitations of attenuation correction in PET-MR are considered when designing research and clinical PET-MR protocols in order to enable accurate quantification of brain PET scans. Whilst the effect of pads is not significant, dense hair, the use of headphones and the use of an independently acquired CT-scan can all lead to non-negligible effects on PET quantification. Although seemingly trivial, these effects add complications to setting up protocols for clinical and research PET-MR studies that do not occur with PET-CT. In the absence of more sophisticated PET-MR brain attenuation correction, the effect of all of the issues above can be minimised if the pragmatic approaches presented in this work are followed.

Modelling clinical decision-making in triage of referrals for extraction.

Introduction: Oral surgery services are progressively moving out of traditional hospital departments and into primary care. This necessitates accurate methods of triaging referrals, so patients of varying complexity are managed in the most suitable environment. The latest NHS commissioning proposal identifies 'level 1' procedures as simple extractions which do not require referral. We developed a model for quantifying how accurately these simple extractions can be predicted from information in standard referral letters. Methods: Experienced clinicians (N = 10) were independently asked to predict whether extractions (N = 25) were likely to be simple-forceps or surgical procedures, from information provided in specially developed standardised referral letters. One oral surgeon had previously completed all extractions. The triaging clinicians were asked to comment on reasons for each decision and state their level of confidence in their predictions. Results: Only 67% (range 52­76%) of extractions were correctly predicted as either simple or surgical with a significant propensity to underestimate the complexity of surgical extractions rather than overestimating simple procedures (p <0.05). High levels of confidence reported by the clinicians in their decisions correlated with more accurate predictions (p <0.05). Conclusions: This is the first attempt to develop a model for clinical decision-making in oral surgery triage services. Our findings suggest there is significant scope for improvement and highlight areas for development.

Sustaining quality in the community: trends in the performance of a structured diabetes care programme in primary care over 16 years.

AIM: To examine the quality of care delivered by a structured primary care-led programme for people with Type 2 diabetes mellitus in 1999-2016. METHODS: The Midland Diabetes Structured Care Programme provides structured primary care-led management. Trends over time in care processes were examined (using a chi-squared trend test and age- and gender-adjusted logistic regression). Screening and annual review attendance were reviewed. A composite of eight National Institute for Health and Care Excellence-recommended processes was used as a quality indicator. Participants who were referred to diabetes nurse specialists were compared with those not referred (Student's t-test, Pearson's chi-squared test, Wilcoxon-Mann-Whitney test). Proportions achieving outcome targets [HbA1c ≤58 mmol/mol (7.5%), blood pressure ≤140/80 mmHg, cholesterol <5.0 mmol/l] were calculated. RESULTS: Data were available for people with diabetes aged ≥18 years: 1998/1999 (n=336); 2003 (n=843); 2008 (n=988); and 2016 (n=1029). Recording of some processes improved significantly over time (HbA1c , cholesterol, blood pressure, creatinine), and in 2016 exceeded 97%. Foot assessment and annual review attendance declined. In 2016, only 29% of participants had all eight National Institute for Health and Care Excellence processes recorded. A higher proportion of people with diabetes who were referred to a diabetes nurse specialist had poor glycaemic control compared with those not referred. The proportions meeting blood pressure and lipid targets increased over time. CONCLUSIONS: Structured primary care led to improvements in the quality of care over time. Poorer recording of some processes, a decline in annual review attendance, and participants remaining at high risk suggest limits to what structured care alone can achieve. Engagement in continuous quality improvement to target other factors, including attendance and self-management, may deliver further improvements.

Thrombolysis for stroke in Ireland: increasing access and maintaining safety in a challenging environment.

BACKGROUND: In the setting of a national audit of acute stroke services, we examined the delivery of thrombolytic therapy for ischaemic stroke and whether current practice was achieving safe outcomes and consistent delivery for patients. METHOD: Data obtained from the recent national stroke audit was compared against previous Irish audit, the most recent SSNAP UK stroke audit and the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) study. RESULTS: Thrombolysis was provided in 27 acute hospitals throughout Ireland during the period assessed with 82% (22/27) providing 24/7 access, the remaining sites using redirect policies. Decision to thrombolyse was made by stroke trained consultants in 63% (17/27) of units, with general physicians and emergency medicine consultants covering the other units. Thrombolysis rate for non-haemorrhagic stroke was 11% (n = 80/742, CI 95% ±2.23) versus a 1% rate in the 2008 audit. Sites receiving patients through a redirect policy had the highest thrombolysis rate, an average of 24%. Nearly 30% of cases were thrombolysed on the weekend. Eighty-three percent of cases were managed in a stroke unit at some time during admission versus 54% of the national total cases. Thirty-seven percent of patients were ≥80 years old. The mortality rate was 11.3% versus the national mortality rate for non-thrombolysed ischaemic strokes of 10% (p > 0.5), and this is comparable to the SITS-MOST 2007 study 3-month mortality rate of 11.3% (p > 0.5). CONCLUSION: Stroke thrombolysis is being effectively and safely provided in acute stroke services in Ireland despite regular involvement of non-specialist staff. There is still potential to improve thrombolysis rate.

Fancy a cup of scald? - The role of hot beverage burns in paediatric burns admissions in Ireland.

Burns and scalds are preventable injuries in children that typically occur in the home. This study aimed to examine the role of hot beverage scalds in paediatric burn admissions in order to identify key target audiences for future safety strategies. Using the Hospital Inpatient Enquiry System (HIPE) a retrospective study of paediatric burn admissions in 2014 examined demographics, cause and severity of injury and location of occurrence. There were 233 paediatric discharges (age 0-18 yrs.) with a principal diagnosis of burn injury; 57% of these occurred in children under three years and 95% of these occurred in the home. Scalds caused 74% of burn injuries; hot beverages accounted for least 33% of these of which 77% were partial thickness and 73% were upper body burns. Effective hot beverage scald prevention strategies, targeted towards caregivers in the home, are required.

FPGA-based RF interference reduction techniques for simultaneous PET-MRI.

The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) as a multi-modal imaging technique is considered very promising and powerful with regard to in vivo disease progression examination, therapy response monitoring and drug development. However, PET-MRI system design enabling simultaneous operation with unaffected intrinsic performance of both modalities is challenging. As one of the major issues, both the PET detectors and the MRI radio-frequency (RF) subsystem are exposed to electromagnetic (EM) interference, which may lead to PET and MRI signal-to-noise ratio (SNR) deteriorations. Early digitization of electronic PET signals within the MRI bore helps to preserve PET SNR, but occurs at the expense of increased amount of PET electronics inside the MRI and associated RF field emissions. This raises the likelihood of PET-related MRI interference by coupling into the MRI RF coil unwanted spurious signals considered as RF noise, as it degrades MRI SNR and results in MR image artefacts. RF shielding of PET detectors is a commonly used technique to reduce PET-related RF interferences, but can introduce eddy-current-related MRI disturbances and hinder the highest system integration. In this paper, we present RF interference reduction methods which rely on EM field coupling-decoupling principles of RF receive coils rather than suppressing emitted fields. By modifying clock frequencies and changing clock phase relations of digital circuits, the resulting RF field emission is optimised with regard to a lower field coupling into the MRI RF coil, thereby increasing the RF silence of PET detectors. Our methods are demonstrated by performing FPGA-based clock frequency and phase shifting of digital silicon photo-multipliers (dSiPMs) used in the PET modules of our MR-compatible Hyperion II (D) PET insert. We present simulations and magnetic-field map scans visualising the impact of altered clock phase pattern on the spatial RF field distribution, followed by MRI noise and SNR scans performed with an operating PET module using different clock frequencies and phase patterns. The methods were implemented via firmware design changes without any hardware modifications. This introduces new means of flexibility by enabling adaptive RF interference reduction optimisations in the field, e.g. when using a PET insert with different MRI systems or when different MRI RF coil types are to be operated with the same PET detector.

Opportunistic screening for atrial fibrillation in a rural area.

INTRODUCTION: Opportunistic screening is an effective means of identifying subjects with Atrial Fibrillation (AF). Previous studies of opportunistic screening have been performed areas with high population density and before the development of novel oral anticoagulant drugs. We performed a study to determine feasibility of AF screening in a predominantly rural, low population density area. METHODS: Over 6 months, subjects 65 years and older were screened by local General Practitioners using radial pulse palpation confirmed by 12 lead Electrocardiogram. Data were recorded electronically and those with newly identified AF were followed up to examine management post diagnosis. RESULTS: In total, 7262 subjects were screened and an irregular pulse was found in 916 (12.6%) of whom 735 (10.1%) had known AF and 55 (0.76%) had newly detected AF. Of these 55 patients with newly documented AF, 28 (50.9%) were women, 38 (69.1%) had hypertension and eight (14.5%) had a smoking history. Mean body mass index in subjects with newly documented AF was 28.9 kg/m(2)(SD 5.6) There was no significant difference in gender mix (P = 0.4), smoking history (P = 0.8) or alcohol history (P = 0.8) with the overall population. Fifty-one (92.7%) subjects had a CHA2DS2VaSC score ≥ 2 of whom 33 (64.7%) were eventually anticoagulated and nine (17.6%) commenced on Aspirin. The rate of newly identified patients in AF was lower than in previous reported key studies because of a higher rate of subjects with known AF. CONCLUSION: Opportunistic AF screening in a rural environment identified a substantial number of new cases, although less than in previous screening studies.

Detecting and estimating head motion in brain PET acquisitions using raw time-of-flight PET data.

Head motion during brain PET imaging is not uncommon and can negatively affect image quality. Motion correction techniques typically either use hardware to prospectively measure head motion, or they divide the acquisition into short fixed-frames and then align and combine these to produce a motion free image. The aim of this work was to retrospectively detect when motion occurred in PET data without the use of motion detection hardware, and then align the frames defined by these motion occurrences. We describe two methods that use either principal component analysis or the motion induced spatial displacements over time to detect motion in raw time-of-flight PET data. The points in time of motion then define the temporal boundaries of frames which are reconstructed without attenuation correction, aligned and combined. Phantom and [18F]-Fallypride patient acquisitions were used to validate and evaluate these approaches, which were compared with motion estimation using 60 s fixed-frames. Both methods identified all motion occurrences in phantom data, and unlike the fixed-frame approach did not exhibit intra-frame motion. With patient acquisitions, images corrected with the motion detection methods increased the average image sharpness by the same amount as the fixed-frame approach, but reduced the number of reconstructions and registrations by a factor of 3.4 on average. Detecting head motion in raw PET data alone is possible, allowing retrospective motion estimation of any listmode brain PET acquisition without additional hardware, subsequently decreasing data processing and potentially reducing intra-frame motion.

Advances, nuances, and potential pitfalls when exploiting the therapeutic potential of RNA interference.

The discovery of RNA interference (RNAi) holds the potential to alter the paradigm of medical therapeutics. With the ability to selectively silence the function of a gene, RNAi not only provides an indispensable research tool for determining the function of a gene, but also offers potential for the development of novel therapeutics that will inhibit specific genes involved in disease. New concepts in therapeutics have been uncovered through the study of RNAi. Nuances have emerged. For instance, global RNAi pathways can be affected by somatic mutations in cancer and cellular stress, such as hypoxia. Also, viral gene therapy can have unexpected effects on endogenous short noncoding RNA pathways. Therefore, it is important to understand where RNAi therapeutics enter the processing pathways. We highlight the evolving use of RNAi as a new class of therapeutics, such as for amyloidosis, and address some of the anticipated challenges associated with its clinical application.

Contrast-enhanced molecular ultrasound differentiates endoglin genotypes in mouse embryos.

Targeted ultrasound contrast imaging has the potential to become a reliable molecular imaging tool. A better understanding of the quantitative aspects of molecular ultrasound technology could facilitate the translation of this technique to the clinic for the purposes of assessing vascular pathology and detecting individual response to treatment. The objective of this study was to evaluate whether targeted ultrasound contrast-enhanced imaging can provide a quantitative measure of endogenous biomarkers. Endoglin, an endothelial biomarker involved in the processes of development, vascular homeostasis, and altered in diseases, including hereditary hemorrhagic telangiectasia type 1 and tumor angiogenesis, was the selected target. We used a parallel plate perfusion chamber in which endoglin-targeted (MBE), rat isotype IgG2 control and untargeted microbubbles were perfused across endoglin wild-type (Eng+/+), heterozygous (Eng+/-) and null (Eng-/-) embryonic mouse endothelial cells and their adhesion quantified. Microbubble binding was also assessed in late-gestation, isolated living transgenic Eng+/- and Eng+/+ embryos. Nonlinear contrast-specific ultrasound imaging performed at 21 MHz was used to collect contrast mean power ratios for all bubble types. Statistically significant differences in microbubble binding were found across genotypes for both in vitro (p<0.05) and embryonic studies (p<0.001); MBE binding was approximately twofold higher in Eng+/+ cells and embryos compared with their Eng+/- counterparts. These results suggest that molecular ultrasound is capable of reliably differentiating between molecular genotypes and relating receptor densities to quantifiable molecular ultrasound levels.

Extracting a respiratory signal from raw dynamic PET data that contain tracer kinetics.

Data driven gating (DDG) methods provide an alternative to hardware based respiratory gating for PET imaging. Several existing DDG approaches obtain a respiratory signal by observing the change in PET-counts within specific regions of acquired PET data. Currently, these methods do not allow for tracer kinetics which can interfere with the respiratory signal and introduce error. In this work, we produced a DDG method for dynamic PET studies that exhibit tracer kinetics. Our method is based on an existing approach that uses frequency-domain analysis to locate regions within raw PET data that are subject to respiratory motion. In the new approach, an optimised non-stationary short-time Fourier transform was used to create a time-varying 4D map of motion affected regions. Additional processing was required to ensure that the relationship between the sign of the respiratory signal and the physical direction of movement remained consistent for each temporal segment of the 4D map. The change in PET-counts within the 4D map during the PET acquisition was then used to generate a respiratory curve. Using 26 min dynamic cardiac NH3 PET acquisitions which included a hardware derived respiratory measurement, we show that tracer kinetics can severely degrade the respiratory signal generated by the original DDG method. In some cases, the transition of tracer from the liver to the lungs caused the respiratory signal to invert. The new approach successfully compensated for tracer kinetics and improved the correlation between the data-driven and hardware based signals. On average, good correlation was maintained throughout the PET acquisitions.

Developing the radiation protection safety culture in the UK.

In the UK, as elsewhere, there is potential to improve how radiological challenges are addressed through improvement in, or development of, a strong radiation protection (RP) safety culture. In preliminary work in the UK, two areas have been identified as having a strong influence on UK society: the healthcare and nuclear industry sectors. Each has specific challenges, but with many overlapping common factors. Other sectors will benefit from further consideration.In order to make meaningful comparisons between these two principal sectors, this paper is primarily concerned with cultural aspects of RP in the working environment and occupational exposures rather than patient doses.The healthcare sector delivers a large collective dose to patients each year, particularly for diagnostic purposes, which continues to increase. Although patient dose is not the focus, it must be recognised that collective patient dose is inevitably linked to collective occupational exposure, especially in interventional procedures.The nuclear industry faces major challenges as work moves from operations to decommissioning on many sites. This involves restarting work in the plants responsible for the much higher radiation doses of the 1960/70s, but also performing tasks that are considerably more difficult and hazardous than those original performed in these plants.Factors which influence RP safety culture in the workplace are examined, and proposals are considered for a series of actions that may lead to an improvement in RP culture with an associated reduction in dose in many work areas. These actions include methods to improve knowledge and awareness of radiation safety, plus ways to influence management and colleagues in the workplace. The exchange of knowledge about safety culture between the nuclear industry and medical areas may act to develop RP culture in both sectors, and have a wider impact in other sectors where exposures to ionising radiations can occur.

Breath metabolomic profiling by nuclear magnetic resonance spectroscopy in asthma.

BACKGROUND: Metabolomic profiling of exhaled breath condensate offers opportunities for the development of noninvasive diagnostics in asthma. We aimed to determine and validate discriminatory metabolomic profiles in adult asthma and to explore profiles in clinically relevant disease phenotypes. METHODS: Nuclear magnetic resonance spectroscopy was used to analyse breath condensate samples from 82 subjects with asthma and 35 healthy volunteers. Multivariate modelling was performed on a 'training set' (70% of the total sample) in order to produce a discriminatory model classifying asthmatics from healthy controls, and the model tested in the remaining subjects. Secondary analyses were performed to determine the models for the identification of asthmatic subgroups based on sputum eosinophilia, neutrophilia, asthma control and inhaled corticosteroid use. RESULTS: A classification model consisting of five discriminating spectral regions was derived using data from the training set with an area under the receiver operating curve (AUROC) of 0.84. In the test set (the remaining 30% of subjects), the AUROC was 0.91, thus providing external validation for the model. The success of the technique for classifying asthma phenotypes was variable, with AUROC for: sputum eosinophilia (3% cut-off) 0.69; neutrophilia (65% cut-off) 0.88; asthma control (cut-off Asthma Control Questionnaire score of 1) 0.63; and inhaled corticosteroid use 0.89. CONCLUSION: Nuclear magnetic resonance spectroscopy of breath condensate successfully differentiates asthmatics from healthy subjects. With identification of the discriminatory compounds, this technique has the potential to provide novel diagnostics and identify novel pathophysiological mechanisms, biomarkers and therapeutic targets.

The effect of regularization in motion compensated PET image reconstruction: a realistic numerical 4D simulation study.

Following continuous improvement in PET spatial resolution, respiratory motion correction has become an important task. Two of the most common approaches that utilize all detected PET events to motion-correct PET data are the reconstruct-transform-average method (RTA) and motion-compensated image reconstruction (MCIR). In RTA, separate images are reconstructed for each respiratory frame, subsequently transformed to one reference frame and finally averaged to produce a motion-corrected image. In MCIR, the projection data from all frames are reconstructed by including motion information in the system matrix so that a motion-corrected image is reconstructed directly. Previous theoretical analyses have explained why MCIR is expected to outperform RTA. It has been suggested that MCIR creates less noise than RTA because the images for each separate respiratory frame will be severely affected by noise. However, recent investigations have shown that in the unregularized case RTA images can have fewer noise artefacts, while MCIR images are more quantitatively accurate but have the common salt-and-pepper noise. In this paper, we perform a realistic numerical 4D simulation study to compare the advantages gained by including regularization within reconstruction for RTA and MCIR, in particular using the median-root-prior incorporated in the ordered subsets maximum a posteriori one-step-late algorithm. In this investigation we have demonstrated that MCIR with proper regularization parameters reconstructs lesions with less bias and root mean square error and similar CNR and standard deviation to regularized RTA. This finding is reproducible for a variety of noise levels (25, 50, 100 million counts), lesion sizes (8 mm, 14 mm diameter) and iterations. Nevertheless, regularized RTA can also be a practical solution for motion compensation as a proper level of regularization reduces both bias and mean square error.

Differences in regional bone metabolism at the spine and hip: a quantitative study using (18)F-fluoride positron emission tomography.

SUMMARY: This study showed that regional bone blood flow and (18)F-fluoride bone plasma clearance measured by positron emission tomography are three times lower at the hip than the lumbar spine. INTRODUCTION: Measurements of effective bone plasma flow (K (1)), bone plasma clearance (K ( i )) and standardised uptake values (SUV) using (18)F-fluoride positron emission tomography ((18)F-PET) provide a useful means of studying regional bone metabolism at different sites in the skeleton. This study compares the regional (18)F-fluoride kinetics and SUV at the hip and lumbar spine (LS). METHODS: Twelve healthy postmenopausal women with no history of metabolic bone disease apart from two with untreated osteoporosis were recruited. Each subject underwent 60-min dynamic (18)F-PET scans at the LS and proximal femur two weeks apart. K (1), K ( i ) and SUV were measured at the LS (mean of L(1)-L(4)), femoral neck (FN), total hip (TH) and femoral shaft (FS). Differences between sites were assessed using the nonparametric Kruskal-Wallis test with a Bonferroni correction for multiple comparisons. RESULTS: Values of K (1), K ( i ) and SUV at the FN, TH and FS were three times lower than at the LS (p = 0.003). Amongst the proximal femur sites, K ( i ) and SUV were lower at the FS compared with the FN and TH, and SUV was lower at the TH compared with the FN (all p < 0.05). The volume of distribution was lower at the TH and FS compared with the LS (p < 0.05). CONCLUSION: The lower values of K (1), K ( i ) and SUV at the hip suggest that lower bone blood flow in the proximal femur is an important factor explaining the principal reason for the differences in bone fluoride kinetics between the LS and hip sites.