Brain PET imaging optimization with time of flight and point spread function modelling

PurposeTo assess the influence of reconstruction algorithms and parameters on the PET image quality of brain phantoms in order to optimize reconstruction for clinical PET brain studies in a new generation PET/CT.MethodsThe 3D Hoffman phantom that simulates ¹⁸F-fluorodeoxyglucose (FDG) distribution was imaged in a Siemens Biograph mCT TrueV PET/CT with Time of Flight (TOF) and Point Spread Function (PSF) modelling. Contrast-to-Noise Ratio (CNR), contrast and noise were studied for different reconstruction models: OSEM, OSEM + TOF, OSEM + PSF and OSEM + PSF + TOF.The 2D multi-compartment Hoffman phantom was filled to simulate 4 different tracers' spatial distribution: FDG, ¹¹C-flumazenil (FMZ), ¹¹C-Methionine (MET) and 6-¹⁸F-fluoro-l-dopa (FDOPA). The best algorithm for each tracer was selected by visual inspection. The maximization of CNR determined the optimal parameters for each reconstruction.ResultsIn the 3D Hoffman phantom, both noise and contrast increased with increasing number of iterations and decreased with increasing FWHM. OSEM + PSF + TOF reconstruction was generally superior to other reconstruction models. Visual analysis of the 2D Hoffman brain phantom suggested that OSEM + PSF + TOF is the optimum algorithm for tracers with focal uptake, such as MET or FDOPA, and OSEM + TOF for tracers with diffuse cortical uptake (i.e. FDG and FMZ). Optimization of CNR demonstrated that OSEM + TOF reconstruction must be performed with 2 iterations and a filter FWHM of 3 mm, and OSEM + PSF + TOF reconstruction with 4 iterations and 1 mm FWHM filter.ConclusionsOptimization of reconstruction algorithm and parameters has been performed to take particular advantage of the last generation PET scanner, recommending specific settings for different brain PET radiotracers.     

Full field spatially-variant image-based resolution modelling reconstruction for the HRRT

Accurate characterisation of the scanner's point spread function across the entire field of view (FOV) is crucial in order to account for spatially dependent factors that degrade the resolution of the reconstructed images. The HRRT users' community resolution modelling reconstruction software includes a shift-invariant resolution kernel, which leads to transaxially non-uniform resolution in the reconstructed images. Unlike previous work to date in this field, this work is the first to model the spatially variant resolution across the entire FOV of the HRRT, which is the highest resolution human brain PET scanner in the world. In this paper we developed a spatially variant image-based resolution modelling reconstruction dedicated to the HRRT, using an experimentally measured shift-variant resolution kernel. Previously, the system response was measured and characterised in detail across the entire FOV of the HRRT, using a printed point source array. The newly developed resolution modelling reconstruction was applied on measured phantom, as well as clinical data and was compared against the HRRT users' community resolution modelling reconstruction, which is currently in use. Results demonstrated improvements both in contrast and resolution recovery, particularly for regions close to the edges of the FOV, with almost uniform resolution recovery across the entire transverse FOV. In addition, because the newly measured resolution kernel is slightly broader with wider tails, compared to the deliberately conservative kernel employed in the HRRT users' community software, the reconstructed images appear to have not only improved contrast recovery (up to 20% for small regions), but also better noise characteristics.     

Laboratory and radiological investigations in general practice. I-Type requested and rate of use.

The use that 30 general practitioners in four group practices made of open access laboratory and radiological facilities was studied for one year. We were particularly interested in whether general practitioners hoped to exclude rather than confirm abnormality when requesting investigations. All but two of the general practitioners studied used investigations to exclude abnormality to a greater extent than to confirm it. The rate at which the practices investigated patients and the number of investigations requested were appreciably different and were different for individual general practitioners, part time general practitioners requesting more investigations than trainees and full time general practitioners. Haematological investigations accounted for over 30% of requests for investigations in all but one practice, biochemical investigations being requested as often as bacteriological investigations in two of the four practices. The ratio of expected to unexpected results varied among general practitioners; no general practitioner had more unexpected results and the range of ratios was similar for full time and part time general practitioners and for trainees. The proportion of patients with abnormalities uncovered by each practice increased disproportionately as the use of investigations increased, supporting a higher rather than lower rate of investigation among general practitioners. Compared with the results of other studies the use of the radiological facilities available was low. X ray examinations of the skeleton were requested more than chest and contrast media examinations by three of the four practices. Most x ray examinations were used to exclude rather than confirm abnormality by all the practices, with over 85% of results confirming the general practitioner''s initial diagnosis.     

Value of Routine Multiple Blood Tests in Patients Attending the General Practitioner

The paper describes the investigation of 296 patients selected at random from those attending the general practitioners'' surgery and studied by means of multiple biochemical and haematological tests. The tests that would not normally have been requested led to a new diagnosis of clinical significance in 16·9% of patients, in most instances requiring an alteration of the patient''s therapy. The effect of the profile tests on patient follow-up, referral of patients to hospital, and the need for subsequent investigations was studied by comparing the patients profiled with a control group of patients not having a blood profile. The place of such an investigation in general practice is considered.     

Use of biochemical profile in children's hospital: results of two controlled trials.

Two controlled trials of the use of a biochemical profile were conducted in a childern''s hospital to see whether the profile led to diagnoses which would not otherwise [have been made and to see what effect it had on the number of extra requests for pathololgical investigations and the length of stay in hospital]. Altogether 2816 children were examined and 13 new diagnoses made. There was a significant increases in the total number of pathorequests but the profile did not alter the length of stay in hospital. We conclude that the profile mad only a small contribtuion to the overall care of the pateints.     

Patients' reactions to their investigations: a study of 504 patients.

Five hundred and four patients who had undergone hospital investigations were interviewed to find out how much information they had been given about the tests; their reactions before, during and after the test; and any after effects. In 74% of cases the tests had been satisfactorily explained. Patients were told more about complicated procedures such as cardiac catherisation than about routine ones such as venepuncture or barium meal examinations. The comments doctors made while performing the investigations were generally reassuring and were only rarely worrying or impatient. About half the patients suffered pain or discomfort during the test and rather more complained of after effects. Only 5% of patients said they would refuse the test again, though 36% said they would agree only reluctantly. Communication lies at the heart of the problem. Hospitals should consider issuing handouts on investigations to back up the doctor''s information and to dispel myths. Staff should be more careful in concealing frightening-looking equipment, and if patients have to wait during investigations it may help reduce their anxiety if they are provided with something to occupy their time.     

Feasibility of using ultra-high field (7 T) MRI for clinical surgical targeting

The advantages of ultra-high magnetic field (7 Tesla) MRI for basic science research and neuroscience applications have proven invaluable. Structural and functional MR images of the human brain acquired at 7 T exhibit rich information content with potential utility for clinical applications. However, (1) substantial increases in susceptibility artifacts, and (2) geometrical distortions at 7 T would be detrimental for stereotactic surgeries such as deep brain stimulation (DBS), which typically use 1.5 T images for surgical planning. Here, we explore whether these issues can be addressed, making feasible the use of 7 T MRI to guide surgical planning. Twelve patients with Parkinson's disease, candidates for DBS, were scanned on a standard clinical 1.5 T MRI and a 7 T MRI scanner. Qualitative and quantitative assessments of global and regional distortion were evaluated based on anatomical landmarks and transformation matrix values. Our analyses show that distances between identical landmarks on 1.5 T vs. 7 T, in the mid-brain region, were less than one voxel, indicating a successful co-registration between the 1.5 T and 7 T images under these specific imaging parameter sets. On regional analysis, the central part of the brain showed minimal distortion, while inferior and frontal areas exhibited larger distortion due to proximity to air-filled cavities. We conclude that 7 T MR images of the central brain regions have comparable distortions to that observed on a 1.5 T MRI, and that clinical applications targeting structures such as the STN, are feasible with information-rich 7 T imaging.     

Optimizing the Magnetization-Prepared Rapid Gradient-Echo (MP-RAGE) Sequence

The three-dimension (3D) magnetization-prepared rapid gradient-echo (MP-RAGE) sequence is one of the most popular sequences for structural brain imaging in clinical and research settings. The sequence captures high tissue contrast and provides high spatial resolution with whole brain coverage in a short scan time. In this paper, we first computed the optimal k-space sampling by optimizing the contrast of simulated images acquired with the MP-RAGE sequence at 3.0 Tesla using computer simulations. Because the software of our scanner has only limited settings for k-space sampling, we then determined the optimal k-space sampling for settings that can be realized on our scanner. Subsequently we optimized several major imaging parameters to maximize normal brain tissue contrasts under the optimal k-space sampling. The optimal parameters are flip angle of 12°, effective inversion time within 900 to 1100 ms, and delay time of 0 ms. In vivo experiments showed that the quality of images acquired with our optimal protocol was significantly higher than that of images obtained using recommended protocols in prior publications. The optimization of k-spacing sampling and imaging parameters significantly improved the quality and detection sensitivity of brain images acquired with MP-RAGE.     

Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells

Background

Chronic lung diseases are a major issue in public health. A serial pulmonary assessment using imaging techniques free of ionizing radiation and which provides early information on local function impairment would therefore be a considerably important development. Magnetic resonance imaging (MRI) is a powerful tool for the static and dynamic imaging of many organs. Its application in lung imaging however, has been limited due to the low water content of the lung and the artefacts evident at air-tissue interfaces. Many attempts have been made to visualize local ventilation using the inhalation of hyperpolarized gases or gadolinium aerosol responding to MRI. None of these methods are applicable for broad clinical use as they require specific equipment.

Methods

We have shown previously that low-field MRI can be used for static imaging of the lung. Here we show that mathematical processing of data derived from serial MRI scans during the respiratory cycle produces good quality images of local ventilation without any contrast agent. A phantom study and investigations in 85 patients were performed.

Results

The phantom study proved our theoretical considerations. In 99 patient investigations good correlation (r = 0.8; p ≤ 0.001) was seen for pulmonary function tests and MR ventilation measurements. Small ventilation defects were visualized.

Conclusion

With this method, ventilation defects can be diagnosed long before any imaging or pulmonary function test will indicate disease. This surprisingly simple approach could easily be incorporated in clinical routine and may be a breakthrough for lung imaging and functional assessment.     

Hormone replacement therapy: a survey of Ontario physicians' prescribing practices

BACKGROUND: Although much has been written about hormone replacement therapy (HRT), there are few clearcut recommendations on its use. The purpose of this study was to determine Ontario physicians'' patterns of and reasons for prescribing HRT, their use of pretreatment investigations and their surveillance of HRT users, and to determine whether physicians'' reported practice is consistent with existing recommendations. METHODS: A self-administered questionnaire was mailed to a nonproportional stratified sample of 327 Ontario physicians (23.9% gynecologists, 76.1% general practitioners/family physicians [GP/FPs]). Outcome measures were ranking of reasons for prescribing HRT, nature of preliminary testing, regimens prescribed, duration of HRT and frequency of follow-up. RESULTS: The response rate was 60.9% overall (70.9% of the gynecologists, 58.3% of the GP/FPs). Prevention of osteoporosis was reported by 97.4% as an important or very important reason for prescribing HRT; prevention of coronary artery disease was important or very important for 89.3%. When considering whether or not to prescribe HRT, 97.3% stated that breast cancer was an important or very important factor. When presented with hypothetical cases, 97.0% stated that they would prescribe combined estrogen-progestin for a symptomatic woman with an intact uterus; 13.6% stated that they would do so for a woman with no uterus. Most reported that they would prescribe HRT for 12 or more years (73.3%) and would follow up patients every 1 to 2 years (70.6%). INTERPRETATION: Despite controversy about HRT in the published literature, the Ontario physicians surveyed reported similar reasons and patterns of prescribing, pretreatment investigations, and surveillance of postmenopausal women using HRT. These results suggest that Ontario physicians'' knowledge about HRT is consistent with recommendations in the published literature.     

Cerebro-afferent vessel and pupillary basal diameter variation induced by stomatognathic trigeminal proprioception: a case report

ABSTRACT: INTRODUCTION: A patient affected by asymmetric hemodynamics of cerebro-afferent vessels underwent duplex color scanner investigations in occlusal proprioceptive un- and rebalance conditions. Pupillometric video-oculographic examinations were performed in order to spot connected trigeminal proprioceptive motor patterns able to interfere on sympathetic autonomic activity. The aim of this case report is to verify if involuntary jaw closing during swallowing, executed in unbalance and rebalance myoelectric activity, would be able to modify cerebral hemodynamics. CASE PRESENTATION: A 56-year-old Caucasian Italian woman affected by asymmetric blood flow of cerebroafferent vessels underwent an electromyographic investigation of her occlusal muscles in order to assess their occlusal functional balance. The extreme asymmetry of myoelectric activity in dental occlusion evidenced by electromyographic values suggested the rebalancing of the functions of occlusal muscles through concurrent transcutaneous stimulation of the trigeminal nerve supra- and submandibular motor branches. The above-mentioned method allowed the detection of a symmetric craniomandibular muscular relation that can be kept constant through the use of a cusp bite modeled on the inferior dental arch: called orthoticsyntropic bite for its peculiar use of electrostimulation. A few days later, the patient underwent a duplex color scanner investigation and pupillometric video-oculographic examinations in occlusal unbalance and rebalance conditions. CONCLUSIONS: A comparative data analysis showed that an unbalanced dental occlusal function may represent an interferential pattern on cerebral hemodynamics velocity and pupillometric evaluations have proved useful both in the analysis of locus coeruleus functional modalities and as a diagnostic tool in the assessment of pathologies involving locus coeruleus and autonomic systems. The inclusion of myoelectric masseter examinations can be useful in patients with asymmetric hemodynamics of cerebro-afferent vessels and dental occlusal proprioceptive rebalance can integrate the complex therapy of patients with increased chronic sympathetic activity.     

Cranial MRI of small rodents using a clinical MR scanner

Increasing numbers of small animal models are in use in the field of neuroscience research. Magnetic resonance imaging (MRI) provides an excellent method for non-invasive imaging of the brain. Using three-dimensional (3D) MR sequences allows lesion volumetry, e.g. for the quantification of tumor size. Specialized small-bore animal MRI scanners are available for high-resolution MRI of small rodents' brain, but major drawbacks of this dedicated equipment are its high costs and thus its limited availability. Therefore, more and more research groups use clinical MR scanners for imaging small animal models. But to achieve a reasonable spatial resolution at an acceptable signal-to-noise ratio with these scanners, some requirements concerning sequence parameters have to be matched. Thus, the aim of this paper was to present in detail a method how to perform MRI of small rodents brain using a standard clinical 1.5 T scanner and clinically available radio frequency coils to keep material costs low and to circumvent the development of custom-made coils.     

Evaluating cost-effectiveness of diagnostic equipment: the brain scanner case.

An approach to evaluating the cost-effectiveness of high-technology diagnostic equipment has been devised, using the introduction of computerised axial tomography (CAT) as a model. With the advent of CAT scanning, angiography and air encephalography have a reduced, though important, role in investigating intracranial disease, and the efficient use of conventional equipment requires the centralisation of neuroradiological services, which would result in major cash savings. In contrast, the pattern of demand for CAT scanning, in addition to the acknowledged clinical efficiency of the scanner and its unique role in the head-injured patient, ephasies the need for improved access to scanners. In the interest of the patients the pattern of service must change.     

Treatment of the terminal stages of breast cancer.

To assess the intensity of and changes in diagnostic investigations and treatment in the terminal stages of breast cancer 555 patients in the area of Tampere University Central Hospital in whom breast cancer had been diagnosed from 1977 to 1980 were followed up for five years. The case notes for the last visit of 519 patients were analysed. The amount of diagnostic activity was similar for those who died and for the survivors. A higher proportion of women who died than of women who survived received treatment at the last follow up visit, and 2.6 times as many of those dying within one week of the last visit were given chemotherapy as were survivors with recurrent disease. Resources devoted to diagnostic investigations and treatment of cancer in terminally ill patients could be better used for care of the patients. This would be more likely to improve the patients'' quality of life and conserve resources.     

Radiation dose around a PET scanner installation: Comparison of Monte Carlo simulations,analytical calculations and experimental results

PurposeMonte Carlo study of radiation transmission around areas surrounding a PET room.MethodsAn extended population of patients administered with ¹⁸F-FDG for PET-CT investigations was studied, collecting air kerma rate and gamma ray spectra measurements at a reference distance. An MC model of the diagnostic room was developed, including the scanner and walls with variable material and thickness. MC simulations were carried out with the widely used code GEANT4.ResultsThe model was validated by comparing simulated radiation dose values and gamma ray spectra produced by a volumetric source with experimental measurements; ambient doses in the surrounding areas were assessed for different combinations of wall materials and shielding and compared with analytical calculations, based on the AAPM Report 108.In the range 1.5–3.0 times of the product between the linear attenuation coefficient and thickness of an absorber (μ x), it was observed that the effectiveness of different combinations of shielding is roughly equivalent. An extensive tabulation of results is given in the text.ConclusionsThe validation tests performed showed a satisfactory agreement between the simulated and expected results. The simulated dose rates incident on, and transmitted by the walls in our model of PET scanner room, are generally in good agreement with analytical estimates performed using the AAPM Publication No. 108 method. This provides an independent confirmation of AAPM's approach. Even in this specific field of application, GEANT4 proved to be a relevant and accurate tool for dosimetry estimates, shielding evaluation and for general radiation protection use.     

The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient''s propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum.A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI.These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI.     

Correlating Behavioral Responses to fMRI Signals from Human Prefrontal Cortex: Examining Cognitive Processes Using Task Analysis

The aim of this methods paper is to describe how to implement a neuroimaging technique to examine complementary brain processes engaged by two similar tasks. Participants'' behavior during task performance in an fMRI scanner can then be correlated to the brain activity using the blood-oxygen-level-dependent signal. We measure behavior to be able to sort correct trials, where the subject performed the task correctly and then be able to examine the brain signals related to correct performance. Conversely, if subjects do not perform the task correctly, and these trials are included in the same analysis with the correct trials we would introduce trials that were not only for correct performance. Thus, in many cases these errors can be used themselves to then correlate brain activity to them. We describe two complementary tasks that are used in our lab to examine the brain during suppression of an automatic responses: the stroop¹ and anti-saccade tasks. The emotional stroop paradigm instructs participants to either report the superimposed emotional ''word'' across the affective faces or the facial ''expressions'' of the face stimuli^1,2. When the word and the facial expression refer to different emotions, a conflict between what must be said and what is automatically read occurs. The participant has to resolve the conflict between two simultaneously competing processes of word reading and facial expression. Our urge to read out a word leads to strong ''stimulus-response (SR)'' associations; hence inhibiting these strong SR''s is difficult and participants are prone to making errors. Overcoming this conflict and directing attention away from the face or the word requires the subject to inhibit bottom up processes which typically directs attention to the more salient stimulus. Similarly, in the anti-saccade task^3,4,5,6, where an instruction cue is used to direct only attention to a peripheral stimulus location but then the eye movement is made to the mirror opposite position. Yet again we measure behavior by recording the eye movements of participants which allows for the sorting of the behavioral responses into correct and error trials⁷ which then can be correlated to brain activity. Neuroimaging now allows researchers to measure different behaviors of correct and error trials that are indicative of different cognitive processes and pinpoint the different neural networks involved.     

Cost of primary health care services in the emergency department and the family physician's office.

An attempt has been made to determine the true cost of providing primary health care for nontraumatic conditions in the emergency departments of two hospitals in Ontario and in the offices of family physicians. A total of 1117 patients presenting with 1 of 10 common symptom/sign complexes at the emergency departments or the offices of 15 participating family physicians were studies with regard to number of visits made, type of assessment by the physician, investigations undertaken, management, therapy and outcome of the illness. Costs were calculated from the charges that would be made against the provincial health services insurance plan and from the system of hospital financing in effect in the province. The average true cost per illness episode of this type of care was $14.63 in hospital A, $14.20 in hospital B and $15.90 in the family physician''s office.     

TEP/TDM dans le diagnostic et la stadification des lymphomes

Histological subtypes of lymphomas are important because FDG uptake is much greater in aggressive than in indolent lymphomas and this, results in lower sensitivity of PET for the staging of indolent lymphomas. Staging is especially useful when treatment is changed according to staging. Staging with imaging methods has traditionally been performed using a CT scanner and has been based on the detection of nodal enlargement, an increased number of small nodes and in the presence of extranodal masses. However, CT is limited by its poor sensitivity in the detection of extranodal sites of involvement, in the identification of tumour involvement of normal size lymph nodes and in the differentiation between malignant and inflammatory enlarged lymph nodes. The uptake of FDG detected with PET images reflects metabolic activity rather than the size of the tissue masses, localizing tumoral activity in enlarged and in normal size lymph nodes. In the literature review that compares PET with CT, PET usually indicates more lesions than CT would and PET improves sensitivity without losing specificity. However, the majority of studies report that PET, improves the staging in a relatively limited number of patients (10-20%) and may change treatment in less than 10% of patients. Diagnostic accuracy of PET may improve with the use of hybrid PET/CT systems that combine metabolic and morphological imaging, in the same scanner and without moving the patient. This is a promising technique that will overcome the limitations of both modalities and may enhance diagnostic accuracy in lymphoma patients. This hybrid equipment allows the use of PET/CT with contrast-enhanced full dose CT (a diagnostic CT) instead of carrying out PET and CT on different days.