Diagnosis and Management of Mild Traumatic Brain Injury in Children: A Systematic Review.

Importance: In recent years, there has been an exponential increase in the research guiding pediatric mild traumatic brain injury (mTBI) clinical management, in large part because of heightened concerns about the consequences of mTBI, also known as concussion, in children. The CDC National Center for Injury Prevention and Control's (NCIPC) Board of Scientific Counselors (BSC), a federal advisory committee, established the Pediatric Mild TBI Guideline workgroup to complete this systematic review summarizing the first 25 years of literature in this field of study. Objective: To conduct a systematic review of the pediatric mTBI literature to serve as the foundation for an evidence-based guideline with clinical recommendations associated with the diagnosis and management of pediatric mTBI. Evidence Review: Using a modified Delphi process, the authors selected 6 clinical questions on diagnosis, prognosis, and management or treatment of pediatric mTBI. Two consecutive searches were conducted on PubMed, Embase, ERIC, CINAHL, and SportDiscus. The first included the dates January 1, 1990, to November 30, 2012, and an updated search included December 1, 2012, to July 31, 2015. The initial search was completed from December 2012 to January 2013; the updated search, from July 2015 to August 2015. Two authors worked in pairs to abstract study characteristics independently for each article selected for inclusion. A third author adjudicated disagreements. The risk of bias in each study was determined using the American Academy of Neurology Classification of Evidence Scheme. Conclusion statements were developed regarding the evidence within each clinical question, and a level of confidence in the evidence was assigned to each conclusion using a modified GRADE methodology. Data analysis was completed from October 2014 to May 2015 for the initial search and from November 2015 to April 2016 for the updated search. Findings: Validated tools are available to assist clinicians in the diagnosis and management of pediatric mTBI. A significant body of research exists to identify features that are associated with more serious TBI-associated intracranial injury, delayed recovery from mTBI, and long-term sequelae. However, high-quality studies of treatments meant to improve mTBI outcomes are currently lacking. Conclusions and Relevance: This systematic review was used to develop an evidence-based clinical guideline for the diagnosis and management of pediatric mTBI. While an increasing amount of research provides clinically useful information, this systematic review identified key gaps in diagnosis, prognosis, and management.

Quantitative PET and SPECT performance characteristics of the Albira Trimodal pre-clinical tomograph.

The Albira Trimodal pre-clinical scanner comprises PET, SPECT and CT sub-systems and thus provides a range of pre-clinical imaging options. The PET component consists of three rings of single-crystal LYSO detectors with axial/transverse fields-of-view (FOVs) of 148/80 mm. The SPECT component has two opposing CsI detectors (100 × 100 mm2) with single-pinhole (SPH) or multi(9)-pinhole (MPH) collimators; the detectors rotate in 6° increments and their spacing can be adjusted to provide different FOVs (25 to 120 mm). The CT sub-system provides 'low' (200 µA, 35 kVp) or 'high' (400 µA, 45 kVp) power x-rays onto a flat-panel CsI detector. This study examines the performance characteristics and quantitative accuracy of the PET and SPECT components. Using the NEMA NU 4-2008 specifications (22Na point source), the PET spatial resolution is 1.5 + 0.1 mm on axis and sensitivity 6.3% (axial centre) and 4.6% (central 70 mm). The usable activity range is ≤ 10 MBq (18F) over which good linearity (within 5%) is obtained for a uniform cylinder spanning the axial FOV; increasing deviation from linearity with activity is, however, observed for the NEMA (mouse) line source phantom. Image uniformity axially is within 5%. Spatial resolution (SPH/MPH) for the minimum SPECT FOV used for mouse imaging (50 mm) is 1.5/1.7 mm and point source sensitivity 69/750 cps MBq­1. Axial uniformity of SPECT images (%CV of regions-of-interest counts along the axis) is mostly within 8% although there is a range of 30­40% for the largest FOV. The variation is significantly smaller within the central 40 mm. Instances of count rate nonlinearity (PET) and axial non-uniformity (SPECT) were found to be reproducible and thus amenable to empirical correction.

Influence of smoking, hypertension, and sex on the phenotypic expression of familial intracranial aneurysms in siblings.

OBJECTIVE: To investigate the effects of smoking, hypertension, and sex on the phenotypic expression of familial intracranial aneurysms (FIAs). METHODS: We retrospectively reviewed the case records of 806 consecutive patients undergoing aneurysm surgery at our institution (1986-1995) and discovered 24 families with at least two affected siblings. Prevalence rates for the smoking, hypertension, and sex risk factors in these nuclear families were compared with those of patients with sporadic intracranial aneurysms (SIAs) and population-based control patients. RESULTS: Affected family members with FIAs exhibited prevalence rates of smoking and hypertension (74% and 43%, respectively) that tended to be higher than those of population-based control patients (52% [P < 0.005] and 36% [P = not significant (NS)], respectively) and comparable to those of patients with SIAs (64% [P = NS] and 40% [P = NS], respectively). A positive association existed between FIA formation and female sex but was somewhat less strong than that observed in the SIAs (59% FIAs, 71% SIAs, 50% control patients). In addition, the prevalence rates of smoking, hypertension, and female sex were higher in affected family members with FIAs than in their unaffected siblings (58% [P < 0.05], 28% [P = 0.06], and 39% [P < 0.05], respectively). Individuals in families with expressed FIAs who had high aneurysmal penetrance had a greater tendency to be smokers, hypertensive, and female (74%, 59%, and 55%, respectively) than did their low-penetrance counterparts (61% [P = 0.1], 27% [P < 0.05], and 45% [P = NS], respectively). CONCLUSION: Together these data suggest that hypertension, smoking, and female sex increase the likelihood that a member of a family with an expressed FIA will have an aneurysm. These observations may prove helpful in guiding the use of screening studies and encouraging education about the potential risks of continued tobacco use and untreated hypertension in this patient cohort.

Effects of 7 years of growth hormone replacement therapy in hypopituitary adults.

Short-term studies of GH replacement in adult hypopituitarism have usually demonstrated beneficial effects on body composition and circulating lipids, with neutral or occasionally adverse effects on glucose tolerance. Fasting hyperinsulinemia has been reported. GH effects on cardiac function have been variable. The effects of long-term GH therapy, taking into account the consequences of increasing age, are not fully known. Thirty-three hypopituitary, initially middle-aged adults were studied over a 7-yr period; 12 patients took GH therapy (mean, 0.7 mg daily) continuously (group A); 11 took GH for only 6-18 months, a minimum of 5 yr previously (group B); and 10 patients never received GH therapy (group C). Other pituitary replacement was maintained. Effects on anthropometry, body composition (by bioimpedance analysis, total body potassium, and dual energy x-ray absorptiometry), circulating lipids, glucose and insulin concentrations, cardiac 2-dimensional and Doppler echocardiography, and exercise tolerance were assessed before and after the treatment period. Continuous GH therapy had no significant effect on body weight, but it prevented the increase in waist circumference and waist to hip ratio that occurred in the patients without GH substitution (waist to hip ratio, group A, 0.87+/-0.08 at baseline, 0.85+/-0.09 at 7 yr; group B, 0.89+/-0.11 at baseline, 0.94+/-0.11 at 7 yr; P < 0.005 for GH effect; group C, 0.87+/-0.10 at baseline, 0.92+/-0.10 at 7 yr; P < 0.005 for GH effect). A GH-induced decrease in subscapular skinfold thickness was also observed. By bioimpedance analysis, GH therapy caused an increase in total body water and fat-free mass, and a decrease in the percent body fat. Although changes occurred with time in all groups, no significant additional GH therapy effects were observed on glucose tolerance, insulin concentrations, lipid levels, cardiac dimensions, echocardiographic diastolic function, or exercise tolerance. In conclusion, prolonged GH substitution in middle-aged hypopituitary adults causes a sustained improvement in body composition. Other benefits, e.g. on lipid levels and exercise tolerance, were not apparent at 7 yr when comparisons were made with GH-untreated hypopituitary controls. Potentially adverse effects on glucose tolerance and insulinemia did not develop with prolonged GH therapy.

Physical characteristics of the ECAT EXACT3D positron tomograph.

The 'EXACT3D' positron tomograph, which is now in routine clinical research use, was developed with the aim of achieving unprecedented sensitivity, high spatial and temporal resolution and simplicity of design using proven detector technology. It consists of six rings of standard detector blocks (CTI/Siemens EXACT HR+) with 4.39 mm x 4.05 mm x 30 mm elements, giving an axial field of view (FOV) of 23.4 cm. This extended FOV and the absence of interplane septa and retractable transmission rod sources has allowed greatly simplified gantry and detector cassette design. Operation in exclusive 3D mode requires an alternative to the conventional coincidence method for transmission scanning, and a single photon approach using a hydraulically driven 137Cs point source has been implemented. The tomograph has no other moving parts. A single time frame of data without any compression is very large (> 300 Mbyte) and two approaches are employed to overcome this difficulty: (a) adjacent sinograms can be summed automatically into different combinations and (b) listmode (event-by-event) acquisition has been instituted, which is both storage efficient (particularly for acquisition of sparse data sets) and maximizes temporal resolution. The high-speed I/O and computing hardware can maintain a sustained acquisition rate of about 4 million coincidence events per second. A disadvantage of the large axial FOV in 3D is the increased sensitivity to activity outside the coincidence FOV. However, this can be minimized by additional side shielding. The mean spatial resolution is 4.8 +/- 0.2 mm FWHM (transaxial, 1 cm off-axis) and 5.6 +/- 0.5 mm (axial, on-axis). Its absolute efficiency is 5.8% for a line source in air (just spanning the axial FOV) and 10% for a central point source (with thresholds of 350-650 keV). For a uniform 20 cm diameter cylinder, the efficiency is 69 kcps kBq(-1) ml(-1) (after subtraction of a scatter fraction of 42%). Sensitivity relative to the EXACT HR+ (with four rings of blocks) is 2.5 (3D) and 12 (2D) times respectively. The rate of random events in blood flow studies in the brain and body, using 15O-labelled water, can be controlled by limiting the administered dose and inserting additional side shielding.

Generation of myocardial factor images directly from the dynamic oxygen-15-water scan without use of an oxygen-15-carbon monoxide blood-pool scan.

UNLABELLED: The measurement of regional myocardial blood flow (MBF) with H2(15)O and PET requires an additional C15O blood-pool scan for the purpose of region of interest (ROI) definition. This additional scan results in a substantially increased radiation dose, study duration and risk of movement artifacts. Therefore, a method was developed to generate myocardial factor images directly from the dynamic H2(15)O study without the need for a C15O scan. METHODS: The factor sinograms were generated by means of linear dimension reduction of the dynamic sinograms, where the required variate and covariate factors (myocardial and blood time-activity curves) were modeled from the lung time-activity curve. The factor images were generated by iterative reconstruction. RESULTS: No significant difference was found between MBF values from ROIs drawn on the traditional images (using the C15O scan) and those drawn on the factor images. CONCLUSION: It is possible to generate myocardial images directly from the dynamic H2(15)O study, so that the C15O scan can be omitted from MBF studies. The proposed method is robust and results in nearly optimal signal-to-noise ratios in the factor images.

Experience with fully 3D PET and implications for future high-resolution 3D tomographs.

The aim of this paper is to report on experience with 3D positron emission tomography (PET) in our institute where we have three 3D scanners, of which two operate exclusively in 3D mode (ECAT ART, EXACT 3D). Fully 3D PET requires attention to a number of factors which are not as problematic in 2D PET. Firstly, 3D tomographs designed for whole-body acquisition suffer from a large single-photon field of view, extending well beyond the coincidence field of view. Single photons from outside the coincidence field of view increase the dead time and random coincidence rates, and contribute scattered events. For brain studies, we have extended the lead side shielding at the ends of the tomograph to mitigate against these effects, and this has dramatically improved the count rate performance. This approach is not as effective for whole-body scanning. In addition, operating in 3D without septa necessitates new approaches to transmission scanning, as measurements using positron emitters such as 68Ge/68Ga have the unfavourable characteristics of high dead time and high scatter. Both of our fully 3D scanners use 137Cs for single-photon transmission measurements, although the data are treated differently. On the ECAT ART, a combination of physical and electronic collimation effectively reduces transmission scatter to acceptable levels. On the EXACT 3D physical collimation is not as readily implemented and therefore segmentation and reassignment of the histogrammed attenuation (mu) values is employed to produce unbiased attenuation correction factors in 3D. Many of the lessons learnt with these BGO (bismuth germanate) based tomographs will be applicable to the next generation of systems using faster detectors such as lutetium oxyorthosilicate (LSO).

The effect of activity outside the direct field of view in a 3D-only whole-body positron tomograph.

The ECAT EXACT3D (CTI/Siemens 966) 3D-only PET tomograph has unprecedented sensitivity due to the large BGO (bismuth germanate) detector volume. However, the consequences of a large (23.4 cm) axial field-of-view (FOV) and the need for a patient port diameter to accommodate body scanning make the device more sensitive to photons arising from activity outside the direct (coincidence) FOV. This leads to relatively higher deadtime and an increased registration of random and scatter (true) coincidences. The purpose of this study is to determine the influence of activity outside the FOV on (i) noise-equivalent counts (NEC) and (ii) the performance of a 'model-based' scatter correction algorithm, and to investigate the effect of side shielding additional to that supplied with the tomograph. Annular shielding designed for brain scanning increased the NEC for blood flow (H[2]15O) measurement (integrated over 120 s) by up to 25%. For 11C tracer studies, the increase is less than 5% over 120 min. Purpose-built additional body shielding, made to conform to the shape of a volunteer, reduced the randoms count rate in a heart blood flow measurement (H[2]15O) by about 30%. After scatter correction the discrepancy between ROI count ratios for compartments within the 20 cm diameter 'Utah' phantom differed by less than 5% from true (sampled) activity concentration ratios. This was so with or without activity outside the FOV and with or without additional side shielding. Count rate performance is thus improved by extra shielding but more improvement is seen in head than in body scanning. Measurement of heart blood flow using bolus injections of H(2)15O would benefit from the use of detectors with lower deadtime and superior timing resolution such as LSO (lutetium oxyorthosilicate).

Calculation of single detector efficiencies and extension of the normalization sinogram in PET.

A fast iterative method is presented for calculating single detector efficiencies for positron emission tomographs. These efficiencies can be used to extend the normalization scan to areas outside that covered by the normalization source. The root mean square (rms) error of the calculated single detector efficiencies decreases exponentially with the number of iterations. Thirty iterations per normalization image are sufficient and take about 1 s on a SUN Classic. The geometry factors are composed of factors which only depend on the distance from the centre of the field-of-view (FOV) and of factors which show a more complex pattern over the normalization sinogram. The geometry factors are specific to each scanner. On the ECAT 931 scanner the complex part of the geometry factors showed a diamond shaped pattern (caused by the varying sensitivity of single detectors in a detector block with varying angle of incidence) and S-shaped curves (representing attenuation caused by supporting rods for the ring source). The coefficient of variation of the diamond-shaped pattern was 4% for detectors farthest from the centre of the FOV. Extensions of the normalization scan may, therefore, contain a relative rms error of about 4% if the applied geometry factors only take the distance from the centre of the FOV into account.

Three-dimensional performance of a small-diameter positron emission tomograph.

Recently, the initial 2D physical characterization of a small-diameter positron emission tomograph, designed specifically for scanning of small laboratory animals, was reported. The physical characteristics of the tomograph operating in 3D mode have now been measured and compared to those obtained in 2D mode. In 3D, the transaxial resolution was measured as 2.4 +/- 0.1 mm full width at half maximum (FWHM) and 6.7 +/- 1.1 mm full width at tenth maximum (FWTM) at the centre of the transaxial field of view (FOV). These values degraded to 4.5 +/- 0.3 mm (tangential) and 6.6 +/- 0.3 mm (radial) FWHM and 10.6 +/- 1.6 mm (tangential) and 11.2 +/- 2.1 mm (radial) FWTM, respectively, at a distance of 40 mm from the centre of the transaxial FOV. The axial resolution was measured as 4.6 +/- 0.1 mm FWHM and 15.0 +/- 0.5 mm FWTM at the centre of the transaxial FOV, increasing to 5.0 +/- 0.1 mm FWHM and 18.8 +/- 3.7 mm FWTM at a radial distance of 40 mm from the centre of the transaxial FOV. These resolutions are similar to those obtained for the tomograph operating in 2D mode. The sensitivity of the tomograph operating in 3D was 4.31 x 10(4) counts s-1 MBq-1 at 250-850 keV compared to 0.995 x 10(4) counts s-1 MBQ-1 in 2D at the same energy thresholds. In this energy window the noise equivalent count rate peaked at 4.1 x 10(4) counts s-1, compared to 1.03 x 10(4) counts s-1 in 2D. A scatter fraction of 30.2% at 250-850 keV was measured for a 18F line source centered in a 60 mm diameter water filled phantom in 3D, compared to 31.0% in 2D for the same scanning geometry and energy thresholds. A comparison was made between 2D and 3D kinetic analyses for a group of five anaesthetized rats scanned using [11C] SCH 23390, a marker of dopamine D1 receptors. The integrity of the results was maintained between 2D and 3D data sets, though in 3D there was a significant reduction in the standard error of the fitted parameter. The results demonstrate that, with regard to sensitivity, there are significant gains in the physical performance of this tomograph when operating in 3D compared to 2D mode and that the quantification of PET studies of small animals using the 3D data reflects this.

ECAT ART - a continuously rotating PET camera: performance characteristics, initial clinical studies, and installation considerations in a nuclear medicine department.

Advances in fully three-dimensional (3D) image reconstruction techniques have permitted the development of a commercial, rotating, partial ring, fully 3D positron emission tomographic (PET) scanner, the ECAT ART. The system has less than one-half the number of bismuth germanate detectors compared with a full ring scanner with the equivalent field of view, resulting in reduced capital cost. The performance characteristics, implications for installation in a nuclear medicine department, and clinical utility of the scanner are presented in this report. The sensitivity (20 cm diameterx20 cm long cylindrical phantom, no scatter correction) is 11400 cps.kBq-1.ml-1. This compares with 5800 and 40500 cps.kBq-1.ml-1 in 2D and 3D respectively for the equivalent full ring scanner (ECAT EXACT). With an energy window of 350-650 keV the maximum noise equivalent count (NEC) rate was 27 kcps at a radioactivity concentration of approximately 15 kBq.ml-1 in the cylinder. Spatial resolution is approximately 6 mm full width at half maximum on axis degrading to just under 8 mm at a distance of 20 cm off axis. Installation and use within the nuclear medicine department does not appreciably increase background levels of radiation on gamma cameras in adjacent rooms and the dose rate to an operator in the same room is 2 microSv. h-1 for a typical fluorine-18 fluorodeoxyglucose (18F-FDG) study with an initial injected activity of 370 MBq. The scanner has been used for clinical imaging with18F-FDG for neurological and oncological applications. Its novel use for imaging iron-52 transferrin for localising erythropoietic activity demonstrates its sensitivity and resolution advantages over a conventional dual-headed gamma camera. The ECAT ART provides a viable alternative to conventional full ring PET scanners without compromising the performance required for clinical PET imaging.

Effect of combined anticoagulation and low-dose aspirin treatment on upper gastrointestinal bleeding.

Multiple studies link the use of nonsteroidal antiinflammatory drugs (NSAIDs) with severe upper gastrointestinal bleeding (UGIB); the incidence of such bleeding is 2-4%. One common regimen to assure patency after intracoronary stent placement requires an anticoagulant (warfarin) combined with aspirin as an antiplatelet agent. However, a 13-fold increase in the risk of UGIB occurs with long-term use of oral anticoagulants and NSAIDs. We retrospectively assessed the rate of UGIB in 138 patients who had received coronary stents (group I, receiving heparin followed by warfarin in combination with aspirin) and 109 angioplasty patients without stents (group II, receiving aspirin alone) between 1990 and 1994. UGIB was identified by hematemesis or melena, which led to gastrointestinal consultation. Patients were analyzed for multiple risk factors. UGIB occurred in 28 of 138 group I patients (20%; 95% CI 13.3-26.7%) and 0 of 109 group II patients (P < 0.0001). Esophagogastroduodenoscopy (EGD) findings on the 28 patients with UGIB included 13 patients with esophagitis or gastritis, 7 patients with gastric or duodenal ulcers, and 8 patients with no identifiable source of bleeding. UGIB occurred within a mean of 2.5 days of initiation of combination therapy. Of patients with UGIB, 10 required blood transfusion (mean number of units = 5.3). Previous history of peptic ulcer disease, smoking, and use of antiulcer medication did not significantly differ between the two groups. The concurrent use of anticoagulant and aspirin in patients with coronary stents creates a significant potential for UGIB and should be used only with extreme caution.

Correction for scatter in 3D brain PET using a dual energy window method.

A method for scatter correction using dual energy window acquisition has been developed and implemented on data collected with a brain-PET tomograph operated in the septa retracted, 3D mode. Coincidence events are assigned to (i) an upper energy window where both photons deposit energy between 380 keV and 850 keV or (ii) a lower energy window where one or both photons deposit within 200 keV and 380 keV. Scaling parameters are derived from measurements of the ratios of counts from line sources due to scattered and unscattered events in the two energy windows in head-sized phantoms. A scaled subtraction of the two energy windows produces a distribution of scatter which is smoothed prior to subtraction from the upper energy window. In phantoms, the correction was found to restore the uniformity, contrast and linearity of activity concentration. Relative activity concentrations were restored to within 7% of their true values in a multicompartment phantom. The method was found to provide accurate correction for scattered events arising from activity outside the direct detector field of view. In a three-compartment phantom containing water, 18F and 11C scanned in dynamic, multiframe mode, the half-lives of the two isotopes were restored to within 2% of their true value.

The design and physical characteristics of a small animal positron emission tomograph.

A small diameter positron emission tomography, designed specifically for small animal studies, was constructed from existing, commercially available, bismuth germanate (BGO) detectors and electronics. The scanner consists of 16 BGO detector blocks arranged to give a tomograph with a diameter of 115 mm and an axial field of view (FOV) of 50 mm. Each block is cut to produce eight (axial) by seven (radial) individual detector elements. The absence of interplane septa enables the acquisition of 3D data sets consisting of 64 sinograms. A 2D data set of 15 sinograms, consisting of eight direct and seven adjacent cross planes, can be extracted from the 3D data set. Images are reconstructed from the 2D sinograms using a conventional filtered backprojection algorithm. Two methods of normalization were investigated, based on either a rotating 68Ge rod source, or a uniform 68Ge plane source, with a uniform cylindrical 18F phantom. Attenuation of the emitted photons was estimated using a rotating 68Ge rod source. The transaxial resolution of the tomograph was measured as 2.3 mm full width at half maximum (FWHM) and 5.6 mm full width at tenth maximum (FWTM) at the centre of the FOV, degrading to 6.6 mm (radial) and 4.4 mm (tangential) FWHM and 10.4 mm (radial) and 14.4 mm (tangential) FWTM at 40.0 mm from the centre of the FOV. The axial slice width was 4.3 mm FWHM, 10.3 mm FWTM at the centre of the transaxial field of view and 4.4 mm FWHM, 10.6 mm FWTM at 20.0 mm from the centre of the FOV. A scatter fraction of 31.0% was measured at 250-850 keV, for an 18F line source centred in a 60 mm diameter, water-filled phantom, reducing to 20.4% and 13.8% as the lower energy discrimination was increased to 380 keV and 450 keV, respectively. The count rate performance was measured using a noise equivalent count rate method, and the linearity of the dead time correction was confirmed over the count rates encountered during routine scanning. In 2D mode, the absolute sensitivity of the tomograph was measured as 9948 counts s-1 MBq-1 at 250-850 keV, 8284 counts s-1 MBq-1 at 380-850 keV and 6280 counts s-1 MBq-1 at 450-850 keV.

Physical performance of a positron tomograph for brain imaging with retractable septa.

Performance characteristics of a new design of positron tomograph with automatically retractable septa for brain imaging have been studied. The device, consisting of block BGO detectors (8 x 8 elements per block), has a ring diameter of 76 cm and an axial FOV of 106.5 mm. The in-plane resolution is on average 5.8 mm and 5.0 mm (FWHM) for stationary and wobble sampling, respectively, over the central 18 cm of the transaxial FOV. Its unique feature is the capability of data acquisition both in the 'conventional' 2D mode (with septa) or 3D mode (septa retracted) where coincidences between any of the 16 detector rings are acquired. When scattered events are subtracted, the efficiency for a 20 cm diameter uniform cylinder increases overall by a factor of 4.8 between 2D (septa extended) and 3D modes. For a 20 cm phantom the trues/singles ratio is higher for 3D than for 2D but for a given unscattered trues rate, the randoms rate in 3D is higher. At 380 keV the scatter fraction within a 20 cm cylinder is 10% (septa extended) and 36% (retracted). In spite of the increase in scatter when septa are retracted, the increased efficiency in the 3D mode of acquisition yields distinct advantages, particularly in the many studies where tracer concentration is low and consequently where dead time and random rates are less important.

Effects of treatments by calcium and sex hormones on vertebral fracturing in osteoporosis.

Lateral radiographs of the thoracic and lumbar spine were taken periodically in 49 patients with osteoporosis. Thirty patients were postmenopausal, and 19 nonmenopausal with osteoporosis due to steroids, male hypogonadism, alcoholism, thyrotoxicosis or unknown cause. Patients were studied before, during and after treatment with high calcium alone, or with combined calcium and sex steroids. Calcium was given as effervescent calcium lactate gluconate, and sex hormones as oestradiol valerate, testosterone oenanthate, or methenolone oenanthate. A total of 964 films covering 409 patient-years were available for measurement. On each vertebra, deformity due to loss of anterior height was measured and assigned to one of four grades. For the time interval between each consecutive pair of films, a patient's vertebral fracture rate score was calculated and expressed per thousand patient-years. In comparison with the corresponding pretreatment fracture rate score, both the postmenopausal and the nonmenopausal groups who had not received sex hormones previously, failed to show significant changes (p = 0.144; p = 0.017) on high calcium alone during mean periods of 4.3 and 2.8 years respectively. If the first 2 years on high calcium were excluded for the postmenopausal group, they still failed to show a reduction in fracture rate score (observed for a mean period of 5.0 years; p = 0.04). When treated with combined calcium and sex hormones, both postmenopausal and nonmenopausal groups showed a lower fracture rate score of 20 and 207 respectively when compared with the pretreatment levels of 1500 and 1697 (in mean treatment periods of 3.2 and 4.4 years; p less than 0.001 in each case). When given high-dose calcium alone, but after treatment with sex hormones as well, the postmenopausal group showed no change in fracture rate score from pretreatment (in a mean of 3.1 years; p = 0.069); however the nonmenopausal group still showed a significant reduction in fracture rate score from 1697 to 42 over a mean period of 2.3 years (p = 0.001). The postmenopausal group, after stopping all treatment, showed a higher fracture rate score of 1286 (in a mean of 2.6 years) than did those on combined calcium and sex hormones, in whom the fracture rate score was 20 (in a mean of 3.2 years; p = 0.008). A subgroup of 11 patients with osteoporosis of both the menopausal and nonmenopausal types, had data both before (in a mean of 5.5 years) and during (for a mean of 2.5 years) treatment with calcium alone; the fracture rate scores were 1473 and 918 (p = 0.247).(ABSTRACT TRUNCATED AT 400 WORDS)

Physical aspects of cardiac scanning with a block detector positron tomograph.

Physical aspects relating to cardiac scanning are described for an eight ring (15 plane) positron tomograph consisting of BGO block detectors (CTI/Siemens 931-08/12). Performance parameters were derived from a cylindrical heart phantom having a "myocardial" wall of thickness varying from 3 mm to 27 mm. This phantom was inserted into a chest phantom consisting of simulated chest wall, lungs, and arms. Recovery coefficients for myocardial thicknesses of 10 mm and 15 mm were 0.75 and 0.9, respectively. Division by the transmission minus "blood pool" (extravascular density) image was found to give a variation of corrected myocardial counts within +/- 5% when transmission data were smoothed. The on-line dead time correction algorithm was found to be accurate to within 5% up to 20 mCi (740 MBq) in the axial field of view (FOV) (10.8 cm) in the central chamber of the heart phantom. However, the correction factor at this rate is approximately 3, which would imply poor use of administered dose. Counts in the image due to scatter are approximately 2% in the (cold) central cavity of the heart phantom relative to counts/pixel in the active myocardium. The presence of phantom arms in the FOV was found to have only a small effect on mean pixel counts and noise in the heart phantom image, as did movement of the arms within a reasonable range.

A method for measuring the absolute sensitivity of positron emission tomographic scanners.

A need exists to measure the absolute sensitivity of a positron emission tomographic (PET) scanner in units of counts.s-1.MBq-1. At present sensitivity is generally determined by measurement of a radionuclide of known concentration distributed in a water-filled cylindrical phantom, usually 20 cm in diameter. The measurement is confounded by self-attenuation of the source and scatter within the cylinder and does not give a true absolute sensitivity measurement. Due to variations in the magnitude and treatment of these factors, meaningful comparison between different manufacturer's scanners is difficult, as are comparisons between different acquisition geometries (e.g. with and without interplane septa present). A method has been developed in our laboratory that provides measurements of absolute sensitivity in air for a scanner independent of attenuation and scatter within the source. The method involves measurements of a thin-line source of fluorine 18 contained within an aluminium housing to which successive aluminium sleeves are added. The extrapolation of these measurements allows an effective counts.s-1.MBq-1 measurement to be made for zero thickness of aluminium. Measurements have yielded absolute sensitivities of 3926 +/- 61 counts.s-1.MBq-1 (0.39% efficiency), 5079 +/- 26 counts.s-1.MBq-1 (0.51%), and 32312 +/- 544 counts.s-1.MBq-1 (3.2%) for a whole-body PET scanner with interplane septa and for a NeuroPET operating with and without interplane septa, respectively.

Experience with the EEC phantom and test procedures in two block detector scanners.

Physical performance characteristics of two modern commercial positron scanners have been compared using a phantom and test procedures defined by the Instrumentation Task Group of the EEC Concerted Action on PET Investigation of Cellular Regeneration and Degeneration. The tomographs were (a) a whole body scanner with 8 detector rings (102 cm diam) and (b) a brain scanner with 16 detector rings (76 cm diam). Each consisted of bismuth germanate block detectors. Both tomographs acquired transaxial image planes with interplane septa inserted but the unique feature of the brain devices is the ability to automatically retract septa and acquire coincidences between the two rings, thus increasing efficiency. Transaxial resolution and recovery coefficients were similar for the two devices, as expected from the equal transaxial detector widths (5.6 mm). With septa, the normalized volume sensitivity (scatter subtracted) was found to be 7% higher for the brain scanner. This reflects the combined effects of different ring diameters, numbers of coincidence lines of response, energy threshold and septa geometry. With septa retracted, the efficiency (scatter subtracted) increases by about a factor of 5. Scatter fractions measured in the reconstructed image were significantly lower than those obtained from sinograms (within the diameter of the phantom). This is indicative of the redistribution of counts in the reconstruction process since total counts are preserved. Count rate tests showed good accuracy of on-line dead time correction schemes at activities (in the FOV) of at least 480 MBq (13 mCi).

Normalisation and reconstruction of PET data acquired by a multi-ring camera with septa retracted.

Emission scan data acquired by a multi-ring PET camera operated with septa retracted must be corrected for (1) geometrical and detector sensitivity variations between the different lines of response (normalisation), (2) photon attenuation, and (3) mispositioned events due to photon scattering. These corrections must be applied to the full 3-D set of lines of response before reconstruction. The standard normalisation and attenuation correction procedures for 2-D scans increase the statistical noise in the emission scan, a problem which becomes even more serious in 3-D because of the large number of LORs involved (approximately 8 million). This paper will describe a fully 3-D reconstruction algorithm for multi-angle PET data incorporating a practical normalisation and attenuation correction procedure which minimises the increase in emission scan statistical noise. The correction factors are derived from 2-D, septa extended scans. The algorithm is currently used to reconstruct 3-D emission data from an ECAT 953B, a sixteen-ring PET camera with retractable septa.