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.

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.

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.

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.

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.

Analysis and comparison of two methods for motion correction in PET imaging.

PURPOSE: Although there have been various proposed methods for positron emission tomography (PET) motion correction, there is not sufficient evidence to answer which method is better in practice. This investigation aims to characterize the behavior of the two main motion-correction approaches in terms of convergence and image properties. METHODS: For the first method, reconstruct-transform-average (RTA), reconstructions of each gate are transformed to a reference gate and averaged. In the second method, motion-compensated image reconstruction (MCIR), motion information is incorporated within the reconstruction. Both techniques studied were based on the ordered subsets expectation maximization algorithm. Motion information was obtained from a dynamic MR acquisition performed on a human volunteer and concurrent PET data were simulated from the dynamic MR data. The two approaches were assessed statistically using multiple realizations to accurately define the noise properties of the reconstructed images. RESULTS: MCIR successfully recovers the true values of all regions, whereas RTA has high bias due to the limited count-statistics and interpolation errors during the transformation step. In addition, RTA noise is very small and stabilized, whereas in MCIR noise becomes progressively greater with the number of iterations and therefore MCIR outperforms RTA in terms of MSE only if noise is treated. For example, MCIR with postfiltering results in MSE up to 42% lower than RTA. CONCLUSIONS: This study indicates that MCIR may provide superior performance overall to RTA if noise is minimized. However, in applications where quantification is not the main objective RTA can be a practical and simple method to correct for motion.

Correlation between Ki-67 immunohistochemistry and 18F-fluorothymidine uptake in patients with cancer: A systematic review and meta-analysis.

BACKGROUND: Positron emission tomography (PET) imaging using the radiotracer 18F-Fluorothymidine (FLT) has been proposed as an imaging biomarker of tumour proliferation. If FLT-PET can be established as such it will provide a non-invasive, quantitative measurement of tumour proliferation across the entire tumour. Results from validation studies have so far been conflicting with some studies confirming a good correlation between FLT uptake and Ki-67 score and others presenting negative results. METHODS: Firstly we performed a systematic review of published studies between 1998 and 2011 that explored the correlation between FLT uptake and Ki-67 score and examined possible variations in the methods used. Studies were eligible if they: (a) included patients with cancer, (b) investigated the correlation between Ki-67 measured by immunohistochemistry and FLT uptake measured with PET scanning, and (c) were published as a full paper in a peer-reviewed scientific journal. Secondly a meta-analysis of the correlation coefficient values reported from each study was performed. Correlation coefficient (r) values were extracted from each study and 95% confidence intervals (CIs) were calculated after applying Fisher's z transformation. For subgroup analysis, studies were classified by the index used to characterise Ki-67 expression (average or maximum expression), the nature of the sample (whole specimen or biopsy) and the cancer type. FINDINGS: Twenty-seven studies were identified as eligible for the meta-analysis. In the studies we examined there were variations in aspects of the methods and reporting. The meta-analysis showed that given an appropriate study design the FLT/Ki-67 correlation is significant and independent of cancer type. Specifically subgroup analysis showed that FLT/Ki-67 correlation was high in studies measuring the Ki-67 average expression regardless of use of surgery or biopsy samples (r=0.70, 95% CI=0.43-0.86, p<0.001). Of the studies that measured Ki-67 maximum expression, only those that used the whole surgical specimen provided a significant r value (r=0.72, 95% CI=0.54-0.84, p<0.001). Studies that used biopsy samples for Ki-67 maximum measurements did not produce a significant r value (r=0.04, 95% CI=-0.18-0.26, p=0.71). In terms of the cancer type subgroup analysis there is sufficient data to support a strong FLT/Ki-67 correlation for brain, lung and breast cancer. No publication bias was detected. INTERPRETATION: This systematic review and meta-analysis highlights the importance of the methods used in validation studies comparing FLT-PET imaging with the biomarker Ki-67. The correlation is significant and independent of cancer type provided a study design that uses Ki-67 average measurements, regardless of nature of sample, or whole surgical samples when measuring Ki-67 maximum expression. Sufficient data to support a strong correlation for brain, lung and breast cancer exist. However, larger, prospective studies with improved study design are warranted to validate these findings for the rest of the cancer types.

Recommendations for the use of PET and PET-CT for radiotherapy planning in research projects.

With the increasing use of positron emission tomography (PET) for disease staging, follow-up and therapy monitoring in a number of oncological indications there is growing interest in the use of PET and PET-CT for radiation treatment planning. In order to create a strong clinical evidence base for this, it is important to ensure that research data are clinically relevant and of a high quality. Therefore the National Cancer Research Institute PET Research Network make these recommendations to assist investigators in the development of radiotherapy clinical trials involving the use of PET and PET-CT. These recommendations provide an overview of the current literature in this rapidly evolving field, including standards for PET in clinical trials, disease staging, volume delineation, intensity modulated radiotherapy and PET-augmented planning techniques, and are targeted at a general audience. We conclude with specific recommendations for the use of PET in radiotherapy planning in research projects.

Thoracic respiratory motion estimation from MRI using a statistical model and a 2-D image navigator.

Respiratory motion models have potential application for estimating and correcting the effects of motion in a wide range of applications, for example in PET-MR imaging. Given that motion cycles caused by breathing are only approximately repeatable, an important quality of such models is their ability to capture and estimate the intra- and inter-cycle variability of the motion. In this paper we propose and describe a technique for free-form nonrigid respiratory motion correction in the thorax. Our model is based on a principal component analysis of the motion states encountered during different breathing patterns, and is formed from motion estimates made from dynamic 3-D MRI data. We apply our model using a data-driven technique based on a 2-D MRI image navigator. Unlike most previously reported work in the literature, our approach is able to capture both intra- and inter-cycle motion variability. In addition, the 2-D image navigator can be used to estimate how applicable the current motion model is, and hence report when more imaging data is required to update the model. We also use the motion model to decide on the best positioning for the image navigator. We validate our approach using MRI data acquired from 10 volunteers and demonstrate improvements of up to 40.5% over other reported motion modelling approaches, which corresponds to 61% of the overall respiratory motion present. Finally we demonstrate one potential application of our technique: MRI-based motion correction of real-time PET data for simultaneous PET-MRI acquisition.

Regional bone metabolism at the lumbar spine and hip following discontinuation of alendronate and risedronate treatment in postmenopausal women.

UNLABELLED: The aim of this study was to examine the effects of bisphosphonate discontinuation on bone metabolism at the spine and hip measured using (18) F-fluoride PET. Bone metabolism at the spine remained stable following discontinuation of alendronate and risedronate at 1 year but increased in the hip in the alendronate group only. INTRODUCTION: Bisphosphonates such as alendronate (ALN) or risedronate (RIS) have persistent effects on spine BMD following discontinuation. METHODS: Positron emission tomography (PET) was used to examine regional bone metabolism in 20 postmenopausal women treated with ALN (n = 11) or RIS (n = 9) for a minimum of 3 years at screening (range 3-9 years, mean 5 years for both groups). Subjects underwent a dynamic scan of the lumbar spine and a static scan of both hips at baseline and 6 and 12 months following treatment discontinuation. (18) F-fluoride plasma clearance (K(i)) at the spine was calculated using a three-compartment model. Standardised uptake values (SUV) were calculated for the spine, total hip, femoral neck and femoral shaft. Measurements of BMD and biochemical markers of bone turnover were also performed. RESULTS: With the exception of a significant decrease in spine BMD in the ALN group, BMD remained stable. Bone turnover markers increased significantly from baseline by 12 months for both study groups. Measurements of K(i) and SUV at the spine and femoral neck did not change significantly in either group. SUV at the femoral shaft and total hip increased significantly but in the ALN group only, increasing by 33.8% (p = 0.028) and 24.0% (p = 0.013), respectively. CONCLUSIONS: Bone metabolism at the spine remained suppressed following treatment discontinuation. A significant increase in SUV at the femoral shaft and total hip after 12 months was observed but for the ALN group only. This study was small, and further clinical studies are required to fully evaluate the persistence of BP treatment.

Fast generation of 4D PET-MR data from real dynamic MR acquisitions.

We have implemented and evaluated a framework for simulating simultaneous dynamic PET-MR data using the anatomic and dynamic information from real MR acquisitions. PET radiotracer distribution is simulated by assigning typical FDG uptake values to segmented MR images with manually inserted additional virtual lesions. PET projection data and images are simulated using analytic forward projections (including attenuation and Poisson statistics) implemented within the image reconstruction package STIR. PET image reconstructions are also performed with STIR. The simulation is validated with numerical simulation based on Monte Carlo (GATE) which uses more accurate physical modelling, but has 150× slower computation time compared to the analytic method for ten respiratory positions and is 7000× slower when performing multiple realizations. Results are validated in terms of region of interest mean values and coefficients of variation for 65 million coincidences including scattered events. Although some discrepancy is observed, agreement between the two different simulation methods is good given the statistical noise in the data. In particular, the percentage difference of the mean values is 3.1% for tissue, 17% for the lungs and 18% for a small lesion. The utility of the procedure is demonstrated by simulating realistic PET-MR datasets from multiple volunteers with different breathing patterns. The usefulness of the toolkit will be shown for performance investigations of the reconstruction, motion correction and attenuation correction algorithms for dynamic PET-MR data.

Establishment of a UK-wide network to facilitate the acquisition of quality assured FDG-PET data for clinical trials in lymphoma.

BACKGROUND: Multicentre trials are required to determine how [fluorine-18]-2-fluoro-2-deoxy-D-glucose-positron emission tomography imaging can guide cancer treatment. Consistency in quality control (QC), scan acquisition and reporting is mandatory for high-quality results, which are comparable across sites. METHODS: A national positron emission tomography (PET) clinical trials network (CTN) has been set up with a 'core laboratory' to coordinate QC and interpret scans. The CTN is involved in trials in Hodgkin's lymphoma [Randomised Phase III trial to determine the role of FDG-PET Imaging in Clinical Stages IA/IIA Hodgkin's Disease (RAPID) and Randomised Phase III trial to assess response adapted therapy using FDG-PET imaging in patients with newly diagnosed, advanced Hodgkin lymphoma (RATHL)] and diffuse large B-cell lymphoma [Blinded evaluation of prognostic value of FDG-PET after 2 cycles of chemotherapy in diffuse large B-cell Non-Hodgkins Lymphoma, a sub-study of the R-CHOP-21 vs R-CHOP-14 trial (R-CHOP PET substudy)]. Approval to join requires scanner validation and agreement to follow a standard QC protocol. Scans are transferred to the core laboratory and reported centrally according to predetermined criteria. RESULTS: The qualification procedure was carried out on 15 scanners. All scanners were able to demonstrate the necessary quantitative accuracy, and following modification of image reconstruction where necessary, scanners demonstrated comparable recovery coefficients (RCs) indicating similar performance. The average RC (±1 standard deviation) was 0.56 ± 0.095 for the 13-mm sphere. Reports from 444 of 473 (94%) patients in RAPID and 67 of 73 (92%) patients in RATHL were available for randomisation of therapy. CONCLUSIONS: The CTN has enabled consistent quality assured PET results to be obtained from multiple centres in time for clinical decision making. The results of trials will be significantly strengthened by this system.

Differential changes in brain glucose metabolism during hypoglycaemia accompany loss of hypoglycaemia awareness in men with type 1 diabetes mellitus. An [11C]-3-O-methyl-D-glucose PET study.

AIMS/HYPOTHESIS: Hypoglycaemia unawareness in type 1 diabetes increases the risk of severe hypoglycaemia and impairs quality of life for people with diabetes. To explore the central mechanisms of hypoglycaemia awareness, we used [11C]-3-O-methyl-D-glucose (CMG) positron emission tomography (PET) to measure changes in global and regional brain glucose metabolism between euglycaemia and hypoglycaemia in aware and unaware diabetic subjects. MATERIALS AND METHODS: Twelve men with type 1 diabetes, of whom six were characterised as aware and six as unaware of hypoglycaemia, underwent two CMG-PET brain scans while plasma glucose was controlled by insulin and glucose infusion either at euglycaemia (5 mmol/l) or at hypoglycaemia (2.6 mmol/l) in random order. RESULTS: With hypoglycaemia, symptoms and sweating occurred only in the aware group. Brain glucose content fell in both groups (p=0.0002; aware, 1.18+/-0.45 to 0.02+/-0.2 mmol/l; unaware, 1.07+/-0.46 to 0.19+/-0.23 mmol/l), with a relative increase in tracer uptake in prefrontal cortical regions, including the anterior cingulate. No detectable differences were found between groups in global brain glucose transport parameters (K1, k2). The cerebral metabolic rate for glucose (CMRglc) showed a relative rise in the aware subjects (11.839+/-2.432 to 13.958+/-2.372) and a fall in the unaware subjects (from 12.457+/-1.938 to 10.16+/-0.801 micromol 100 g(-1) min(-1), p=0.043). CONCLUSIONS/INTERPRETATION: Hypoglycaemia is associated with reduced brain glucose content in aware and unaware subjects, with a relative preservation of metabolism in areas associated with sympathetic activation. The relative rise in global glucose metabolic rate seen in aware subjects during hypoglycaemia contrasted with the relative fall in the unaware subjects and suggests that cortical neuronal activation is a necessary correlate of the state of hypoglycaemia awareness.

An improved analytical detector response function model for multilayer small-diameter PET scanners.

The optimization of spatial resolution is a critical consideration in the design of small-diameter positron emission tomography (PET) scanners for animal imaging, and is often addressed with Monte Carlo simulations. As a faster and simpler solution, we have developed a new analytical model of the PET detector response function, and implemented the model for a small single-slice, multilayer PET scanner. The accuracy of the model has been assessed by comparison with both Monte Carlo simulations and experimental measurements published in the literature. Results from the analytical model agreed well with the Monte Carlo method, being noise free and two to three orders of magnitude faster. The only major discrepancy was a slight underestimation of the width of the point spread function by the analytical method as inter-crystal scatter is neglected. We observed good agreement between the predictions of the model and experimental measurements. For two large-diameter scanners additional discrepancies were seen due to photon acollinearity, which is not considered in the model. We have shown that the simple and fast analytical detector response function model can provide accurate estimates of spatial resolution for small-diameter PET scanners, and could be a useful tool for several applications, complementing or cross-validating other simulation methods.

Quantification of skeletal kinetic indices in Paget's disease using dynamic 18F-fluoride positron emission tomography.

The purpose of this study was to quantify indices of regional bone metabolism in Paget's disease and to compare these indices with normal bone using dynamic 18F-fluoride positron emission tomography (PET). Seven patients with vertebral Paget's disease had 1 h dynamic 18F-fluoride PET scans performed. The scans included a diseased vertebra and an adjacent normal vertebra. Arterial plasma input functions were also measured. A three-compartment, four-parameter model was used with nonlinear regression analysis to estimate bone kinetic variables. Compared with normal bone, pagetic bone demonstrated higher values of plasma clearance to bone mineral (Ki; 1.03 x 10(-1) vs. 0.36 x 10(-1) ml/min per milliliter; p = 0.018) and clearance to total bone tissue (K1; 2.38 x 10(-1) vs. 1.25 x 10(-1) ml/min per milliliter; p = 0.018), reflecting increased mineralization and blood flow, respectively. Release of 18F-fluoride from bone mineral (k4) was lower in pagetic bone (p = 0.022), suggesting tighter binding of 18F-fluoride to bone mineral. The notional volume of the extravascular bone compartment (K1/k2) was greater in pagetic bone (p = 0.018). Although the unidirectional extraction efficiency from the extravascular space to bone mineral (Ki/K1) was greater in pagetic bone (p = 0.018), a lower pagetic value of k2 (p = 0.028), describing the rate of transfer from the bone extravascular compartment to plasma, suggests that the 18F-fluoride that enters the relatively fibrotic marrow space of pagetic bone may be less accessible for return to plasma. These findings confirm some of the known pathophysiology of Paget's disease, introduce some new observations, and show how dynamic 18F-fluoride PET may be of value in the measurement of regional metabolic parameters in focal bone disorders.

Changes in regional brain (18)F-fluorodeoxyglucose uptake at hypoglycemia in type 1 diabetic men associated with hypoglycemia unawareness and counter-regulatory failure.

We examined the effects of acute moderate hypoglycemia and the condition of hypoglycemia unawareness on regional brain uptake of the labeled glucose analog [(18)F]fluorodeoxyglucose (FDG) using positron emission tomography (PET). FDG-PET was performed in diabetic patients with (n = 6) and without (n = 7) hypoglycemia awareness. Each patient was studied at plasma glucose levels of 5 and 2.6 mmol/l, applied by glucose clamp techniques, in random order. Hypoglycemia-unaware patients were asymptomatic during hypoglycemia, with marked attenuation of their epinephrine responses (mean [+/- SD] peak of 0.77 +/- 0.39 vs. 7.52 +/- 2.9 nmol/l; P < 0.0003) and a reduced global brain FDG uptake ([mean +/- SE] 2.592 +/- 0.188 vs. 2.018 +/- 0.174 at euglycemia; P = 0.027). Using statistical parametric mapping (SPM) to analyze images of FDG uptake, we identified a subthalamic brain region that exhibited significantly different behavior between the aware and unaware groups. In the aware group, there was little change in the normalized FDG uptake in this region in response to hypoglycemia ([mean +/- SE] 0.654 +/- 0.016 to 0.636 +/- 0.013; NS); however, in the unaware group, the uptake in this region fell from 0.715 +/- 0.015 to 0.623 +/- 0.012 (P = 0.001). Our data were consistent with the human hypoglycemia sensor being anatomically located in this brain region, and demonstrated for the first time a change in its metabolic function associated with the failure to trigger a counter-regulatory response.

Effect of corrections for blood glucose and body size on [18F]FDG PET standardised uptake values in lung cancer.

Standardised uptake values (SUVs) are commonly used as a semi-quantitative index of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) tracer uptake in positron emission tomography (PET). Studies have shown that SUVs may depend on body size and blood glucose concentration and corrections for these effects have been proposed in the literature. This retrospective study investigated the effect of the proposed corrections on SUVs from a group of 154 patients with lung cancer who had scans on a dedicated PET scanner. A total of 252 SUVs were requested as an aid to staging during consideration for surgical resection. SUVs were calculated normalised to body weight (SUVw), lean body mass (SUV(LBM)) and body surface area (SUV(BSA)). The following correlations were examined: SUV with height, weight and body surface area for the different body size normalisations; SUVw and SUVw x blood glucose (SUV(BG)) with blood glucose; SUVw with scan time post injection; and SUVw with apparent lesion diameter. Significant correlations were only observed between: SUV(LBM) and height (P=0.007); SUVw and scan time (P=0.007); SUVw and lesion diameter (P=0.0005); and SUV(BG) and blood glucose (P<0.00001). The correlation between SUV(LBM) and height suggests that lean body mass as a function of height alone should not be used to normalise SUVs; however, the lean body mass calculated from a height and weight nomogram did not show this effect. The strong correlation between SUV(BG) and blood glucose concentration suggests that for non-diabetic fasted patients, lung tumour SUVs should not be adjusted for blood glucose.