A multicentre simulation study of planar whole-body bone scintigraphy in Sweden.

BACKGROUND: Whole-body bone scintigraphy is a clinically useful non-invasive and highly sensitive imaging method enabling detection of metabolic changes at an early stage of disease, often earlier than with conventional radiologic procedures. Bone scintigraphy is one of the most common nuclear medicine methods used worldwide. Therefore, it is important that the examination is implemented and performed in an optimal manner giving the patient added value in the subsequent care process. The aim of this national multicentre survey was to investigate Swedish nuclear medicine departments compliance with European practice guidelines for bone scintigraphy. In addition, the effect of image acquisition parameters on the ability to detect metabolic lesions was investigated. METHODS: Twenty-five hospital sites participated in the study. The SIMIND Monte Carlo (MC) simulation and the XCAT phantom were used to simulate ten fictive patient cases with increased metabolic activity distributed at ten different locations in the skeleton. The intensity of the metabolic activity was set into six different levels. Individual simulations were performed for each site, corresponding to their specific camera system and acquisition parameters. Simulated image data sets were then sent to each site and were visually evaluated in terms of if there was one or several locations with increased metabolic activity relative to normal activity. RESULT: There is a high compliance in Sweden with the EANM guidelines regarding image acquisition parameters for whole-body bone scintigraphy. However, up to 40% of the participating sites acquire lower count density in the images than recommended. Despite this, the image quality was adequate to maintain a stable detection level. None of the hospital sites or individual responders deviated according to the statistical analysis. There is a need for at least 2.5 times metabolic activity compared to normal for a lesion to be detected. CONCLUSION: The imaging process is well harmonized throughout the country and there is a high compliance with the EANM guidelines. There is a need for at least 2.5 times the normal metabolic activity for a lesion to be detected as abnormal.

Cyclotron-produced 68Ga from enriched 68Zn foils.

The growing need and limited availability of generator produced 68Ga (T1/2 = 68 min) for PET has provided the impetus for alternative, high output, 68Ga production routes such as charge particle activation of enriched 68Zn using PET cyclotrons. The work presents a rapid production method for clinically useful 68Ga for radiolabeling. The focus is also to expand the production capacity of cyclotron solid target-produced 68Ga over generator produced and liquid solutions targets by using enriched 68Zn-foils that minimizes target preparation.

Diagnostic performance of the specific uptake size index for semi-quantitative analysis of I-123-FP-CIT SPECT: harmonized multi-center research setting versus typical clinical single-camera setting.

INTRODUCTION: The specific uptake size index (SUSI) of striatal FP-CIT uptake is independent of spatial resolution in the SPECT image, in contrast to the specific binding ratio (SBR). This suggests that the SUSI is particularly appropriate for multi-site/multi-camera settings in which camera-specific effects increase inter-subject variability of spatial resolution. However, the SUSI is sensitive to inter-subject variability of striatum size. Furthermore, it might be more sensitive to errors of the estimate of non-displaceable FP-CIT binding. This study compared SUSI and SBR in the multi-site/multi-camera (MULTI) setting of a prospective multi-center study and in a mono-site/mono-camera (MONO) setting representative of clinical routine. METHODS: The MULTI setting included patients with Parkinson's disease (PD, n = 438) and healthy controls (n = 207) from the Parkinson Progression Marker Initiative. The MONO setting included 122 patients from routine clinical patient care in whom FP-CIT SPECT had been performed with the same double-head SPECT system according to the same acquisition and reconstruction protocol. Patients were categorized as "neurodegenerative" (n = 84) or "non-neurodegenerative" (n = 38) based on follow-up data. FP-CIT SPECTs were stereotactically normalized to MNI space. SUSI and SBR were computed for caudate, putamen, and whole striatum using unilateral ROIs predefined in MNI space. SUSI analysis was repeated in native patient space in the MONO setting. The area (AUC) under the ROC curve for identification of PD/"neurodegenerative" cases was used as performance measure. RESULTS: In both settings, the highest AUC was achieved by the putamen (minimum over both hemispheres), independent of the semi-quantitative method (SUSI or SBR). The putaminal SUSI provided slightly better performance with ROI analysis in MNI space compared to patient space (AUC = 0.969 vs. 0.961, p = 0.129). The SUSI (computed in MNI space) performed slightly better than the SBR in the MULTI setting (AUC = 0.993 vs. 0.991, p = 0.207) and slightly worse in the MONO setting (AUC = 0.969 vs. AUC = 0.976, p = 0.259). There was a trend toward larger AUC difference between SUSI and SBR in the MULTI setting compared to the MONO setting (p = 0.073). Variability of voxel intensity in the reference region was larger in misclassified cases compared to correctly classified cases for both SUSI and SBR (MULTI setting: p = 0.007 and p = 0.012, respectively). CONCLUSIONS: The SUSI is particularly useful in MULTI settings. SPECT images should be stereotactically normalized prior to SUSI analysis. The putaminal SUSI provides better diagnostic performance than the SUSI of the whole striatum. Errors of the estimate of non-displaceable count density in the reference region can cause misclassification by both SUSI and SBR, particularly in borderline cases. These cases might be identified by visual checking FP-CIT uptake in the reference region for particularly high variability.

Brain Glucose Metabolism Heterogeneity in Idiopathic REM Sleep Behavior Disorder and in Parkinson's Disease.

BACKGROUND/OBJECTIVE: Idiopathic REM sleep behavior disorder (iRBD) often precedes Parkinson's disease (PD) and other alpha-synucleinopathies. The aim of the study is to investigate brain glucose metabolism of patients with RBD and PD by means of a multidimensional scaling approach, using18F-FDG-PET as a biomarker of synaptic function. METHODS: Thirty-six iRBD patients (64.1±6.5 y, 32 M), 72 PD patients, and 79 controls (65.6±9.4 y, 53 M) underwent brain 18F-FDG-PET. PD patients were divided according to the absence (PD, 32 subjects; 68.4±8.5 y, 15 M) or presence (PDRBD, 40 subjects; 71.8±6.6 y, 29 M) of RBD. 18F-FDG-PET scans were used to independently discriminate subjects belonging to four categories: controls (RBD no, PD no), iRBD (RBD yes, PD no), PD (RBD no, PD yes) and PDRBD (RBD yes, PD yes). RESULTS: The discriminant analysis was moderately accurate in identifying the correct category. This is because the model mostly confounds iRBD and PD, thus the intermediate classes. Indeed, iRBD, PD and PDRBD were progressively located at increasing distance from controls and are ordered along a single dimension (principal coordinate analysis) indicating the presence of a single flux of variation encompassing both RBD and PD conditions. CONCLUSION: Data-driven approach to brain 18F-FDG-PET showed only moderate discrimination between iRBD and PD patients, highlighting brain glucose metabolism heterogeneity among such patients. iRBD should be considered as a marker of an ongoing condition that may be picked-up in different stages across patients and thus express different brain imaging features and likely different clinical trajectories.

Head-to-Head Comparison among Semi-Quantification Tools of Brain FDG-PET to Aid the Diagnosis of Prodromal Alzheimer's Disease.

BACKGROUND: Several automatic tools have been implemented for semi-quantitative assessment of brain [18]F-FDG-PET. OBJECTIVE: We aimed to head-to-head compare the diagnostic performance among three statistical parametric mapping (SPM)-based approaches, another voxel-based tool (i.e., PALZ), and a volumetric region of interest (VROI-SVM)-based approach, in distinguishing patients with prodromal Alzheimer's disease (pAD) from controls. METHODS: Sixty-two pAD patients (MMSE score = 27.0±1.6) and one hundred-nine healthy subjects (CTR) (MMSE score = 29.2±1.2) were enrolled in five centers of the European Alzheimer's Disease Consortium. The three SPM-based methods, based on different rationales, included 1) a cluster identified through the correlation analysis between [18]F-FDG-PET and a verbal memory test (VROI-1), 2) a VROI derived from the comparison between pAD and CTR (VROI-2), and 3) visual analysis of individual maps obtained by the comparison between each subject and CTR (SPM-Maps). The VROI-SVM approach was based on 6 VROI plus 6 VROI asymmetry values derived from the pAD versus CTR comparison thanks to support vector machine (SVM). RESULTS: The areas under the ROC curves between pAD and CTR were 0.84 for VROI-1, 0.83 for VROI-2, 0.79 for SPM maps, 0.87 for PALZ, and 0.95 for VROI-SVM. Pairwise comparisons of Youden index did not show statistically significant differences in diagnostic performance between VROI-1, VROI-2, SPM-Maps, and PALZ score whereas VROI-SVM performed significantly (p < 0.005) better than any of the other methods. CONCLUSION: The study confirms the good accuracy of [18]F-FDG-PET in discriminating healthy subjects from pAD and highlights that a non-linear, automatic VROI classifier based on SVM performs better than the voxel-based methods.

Accuracy and generalization capability of an automatic method for the detection of typical brain hypometabolism in prodromal Alzheimer disease.

PURPOSE: The aim of this study was to verify the reliability and generalizability of an automatic tool for the detection of Alzheimer-related hypometabolic pattern based on a Support-Vector-Machine (SVM) model analyzing 18F-fluorodeoxyglucose (FDG) PET data. METHODS: The SVM model processed metabolic data from anatomical volumes of interest also considering interhemispheric asymmetries. It was trained on a homogeneous dataset from a memory clinic center and tested on an independent multicentric dataset drawn from the Alzheimer's Disease Neuroimaging Initiative. Subjects were included in the study and classified based on a diagnosis confirmed after an adequate follow-up time. RESULTS: The accuracy of the discrimination between patients with Alzheimer Disease (AD), in either prodromal or dementia stage, and normal aging subjects was 95.8%, after cross-validation, in the training set. The accuracy of the same model in the testing set was 86.5%. The role of the two datasets was then reversed, and the accuracy was 89.8% in the multicentric training set and 88.0% in the monocentric testing set. The classification rate was also evaluated in different subgroups, including non-converter mild cognitive impairment (MCI) patients, subjects with MCI reverted to normal conditions and subjects with non-confirmed memory concern. The percent of pattern detections increased from 77% in early prodromal AD to 91% in AD dementia, while it was about 10% for healthy controls and non-AD patients. CONCLUSIONS: The present findings show a good level of reproducibility and generalizability of a model for detecting the hypometabolic pattern in AD and confirm the accuracy of FDG-PET in Alzheimer disease.

The Alzheimer's disease metabolic brain pattern in mild cognitive impairment.

We investigated the expression of the Alzheimer's disease-related metabolic brain pattern (ADRP) in 18F-FDG-PET scans of 44 controls, 27 patients with mild cognitive impairment (MCI) who did not convert to Alzheimer's disease (AD) after five or more years of clinical follow-up, 95 MCI patients who did develop AD dementia on clinical follow-up, and 55 patients with mild-to-moderate AD. The ADRP showed good sensitivity (84%) and specificity (86%) for MCI-converters when compared to controls, but limited specificity when compared to MCI non-converters (66%). Assessment of 18F-FDG-PET scans on a case-by-case basis using the ADRP may be useful for quantifying disease progression.

Emerging clinical issues and multivariate analyses in PET investigations.

PET using 18F-2-fluoro-2-deoxy-D-glucose (FDG-PET) has been gradually introduced in the diagnostic clinical criteria of the most prevalent neurodegenerative diseases. Moreover, an increasing amount of literature has shown that the information provided by FDG-PET enhances the sensitivity of standard imaging biomarkers in less frequent disorders in which an early differential diagnosis can be of paramount relevance for patient management and outcome. Therefore emerging uses of FDG-PET may be important in prion diseases, autoimmune encephalitis (AE) and amyotrophic lateral sclerosis. Interestingly, FDG-PET findings can also be observed in the early phases of these conditions, even in the presence of normal magnetic resonance imaging scans. Thalamic hypometabolism is a common finding in sporadic Creutzfeldt-Jacob disease and fatal familiar insomnia patients, with further cortical synaptic dysfunction in the former. Limbic and extra-limbic metabolic abnormalities (more often hypermetabolism) can be observed in AE, although specific patterns may be seen within different syndromes associated with antibodies that target neuronal surface or synaptic antigens. FDG-PET shows its usefulness by discriminating patients with amyotrophic lateral sclerosis associated to upper motor neuron onset that evolve to frontotemporal dementia. Besides visual and voxel based image analysis, multivariate analysis as interregional correlation analysis and independent/principal component analysis have been successfully implemented to PET images increasing the accuracy of the discrimination of neurodegenerative diseases. The clinical presentation and current diagnostic criteria of these neurologic disorders as well as the emerging usefulness of FDG-PET in the diagnostic workup are presented and discussed in this review.

Early identification of MCI converting to AD: a FDG PET study.

PURPOSE: Mild cognitive impairment (MCI) is a transitional pathological stage between normal ageing (NA) and Alzheimer's disease (AD). Although subjects with MCI show a decline at different rates, some individuals remain stable or even show an improvement in their cognitive level after some years. We assessed the accuracy of FDG PET in discriminating MCI patients who converted to AD from those who did not. METHODS: FDG PET was performed in 42 NA subjects, 27 MCI patients who had not converted to AD at 5 years (nc-MCI; mean follow-up time 7.5 ± 1.5 years), and 95 MCI patients who converted to AD within 5 years (MCI-AD; mean conversion time 1.8 ± 1.1 years). Relative FDG uptake values in 26 meta-volumes of interest were submitted to ANCOVA and support vector machine analyses to evaluate regional differences and discrimination accuracy. RESULTS: The MCI-AD group showed significantly lower FDG uptake values in the temporoparietal cortex than the other two groups. FDG uptake values in the nc-MCI group were similar to those in the NA group. Support vector machine analysis discriminated nc-MCI from MCI-AD patients with an accuracy of 89% (AUC 0.91), correctly detecting 93% of the nc-MCI patients. CONCLUSION: In MCI patients not converting to AD within a minimum follow-up time of 5 years and MCI patients converting within 5 years, baseline FDG PET and volume-based analysis identified those who converted with an accuracy of 89%. However, further analysis is needed in patients with amnestic MCI who convert to a dementia other than AD.

Progressive Disintegration of Brain Networking from Normal Aging to Alzheimer Disease: Analysis of Independent Components of 18F-FDG PET Data.

Brain connectivity has been assessed in several neurodegenerative disorders investigating the mutual correlations between predetermined regions or nodes. Selective breakdown of brain networks during progression from normal aging to Alzheimer disease dementia (AD) has also been observed. Methods: We implemented independent-component analysis of 18F-FDG PET data in 5 groups of subjects with cognitive states ranging from normal aging to AD-including mild cognitive impairment (MCI) not converting or converting to AD-to disclose the spatial distribution of the independent components in each cognitive state and their accuracy in discriminating the groups. Results: We could identify spatially distinct independent components in each group, with generation of local circuits increasing proportionally to the severity of the disease. AD-specific independent components first appeared in the late-MCI stage and could discriminate converting MCI and AD from nonconverting MCI with an accuracy of 83.5%. Progressive disintegration of the intrinsic networks from normal aging to MCI to AD was inversely proportional to the conversion time. Conclusion: Independent-component analysis of 18F-FDG PET data showed a gradual disruption of functional brain connectivity with progression of cognitive decline in AD. This information might be useful as a prognostic aid for individual patients and as a surrogate biomarker in intervention trials.

Can Spatiotemporal Fluoride (18F-) Uptake be Used to Assess Bone Formation in the Tibia? A Longitudinal Study Using PET/CT.

BACKGROUND: When a bone is broken for any reason, it is important for the orthopaedic surgeon to know how bone healing is progressing. There has been resurgence in the use of the fluoride (18F-) ion to evaluate various bone conditions. This has been made possible by availability of positron emission tomography (PET)/CT hybrid scanners together with cyclotrons. Absorbed on the bone surface from blood flow, 18F- attaches to the osteoblasts in cancellous bone and acts as a pharmacokinetic agent, which reflects the local physiologic activity of bone. This is important because it shows bone formation indicating that the bone is healing or no bone formation indicating no healing. As 18F- is extracted from blood in proportion to blood flow and bone formation, it thus enables determination of bone healing progress. QUESTIONS/PURPOSES: The primary objective of this study was to determine whether videos showing the spatiotemporal uptake of 18F- via PET bone scans could show problematic bone healing in patients with complex tibia conditions. A secondary objective was to determine if semiquantification of radionuclide uptake was consistent with bone healing. METHODS: This study investigated measurements of tibia bone formation in patients with complex fractures, osteomyelitis, and osteotomies treated with a Taylor Spatial FrameTM (TSF) by comparing clinical healing progress with spatiotemporal fluoride (18F-) uptake and the semiquantitative standardized uptake value (SUV). This procedure included static and dynamic image acquisition. For intrapatient volumes acquired at different times, the CT and PET data were spatially registered to bring the ends of the bones that were supposed to heal into alignment. To qualitatively observe how and where bone formation was occurring, time-sequenced volumes were reconstructed and viewed as a video. To semiquantify the uptake, the mean and maximum SUVs (SUVmean, SUVmax) were calculated for the ends of the bones that were supposed to heal and for normal bone, using a spherical volume of interest drawn on the registered volumes. To make the semiquantitative data comparable for all patients with multiple examinations, the SUVmean and SUVmax difference per day (SUVmeanDPD and SUVmaxDPD) between the first PET/CT scan and each subsequent one was calculated. Indicators of poor healing progress were (1) uneven distribution of the radionuclide uptake between ends of the bones that were supposed to heal as seen in the video or, (2) low absolute magnitude of the SUV difference data. Twenty-four patients treated between October 2013 and April 2015 with a TSF gave informed consent to be examined with 18F- PET/CT bone scans. Twenty-two patients successfully completed treatment, one of whom had only one PET/CT scan. RESULTS: Observation of 18F- uptake was able to identify three patients whose healing progress was poor, indicated by uneven distribution of radionuclide uptake across the ends of the bones that were supposed to heal. An absolute magnitude of the SUVmaxDPD of 0.18 or greater indicated good bone formation progress. This was verified in 10 patients by the days between the operation to attach and to remove the TSF being less than 250 days, whereas other SUVmaxDPD values were ambiguous, with 11 patients achieving successful completion. CONCLUSIONS: Observation of the spatiotemporal uptake of 18F- appears to be a promising method to enable the clinician to assess the progress of bone formation in different parts of the bone. Bone uptake which is uneven across the ends of bone that were supposed to heal or very low bone uptake might indicate impaired bone healing where early intervention may then be needed. However, semiquantification of 18F- uptake (SUVmaxDPD), SUVmeanDPD) was ambiguous in showing consistency with the bone-healing progress. LEVEL OF EVIDENCE: Level III, diagnostic study.

[123I]FP-CIT ENC-DAT normal database: the impact of the reconstruction and quantification methods.

BACKGROUND: [123I]FP-CIT is a well-established radiotracer for the diagnosis of dopaminergic degenerative disorders. The European Normal Control Database of DaTSCAN (ENC-DAT) of healthy controls has provided age and gender-specific reference values for the [123I]FP-CIT specific binding ratio (SBR) under optimised protocols for image acquisition and processing. Simpler reconstruction methods, however, are in use in many hospitals, often without implementation of attenuation and scatter corrections. This study investigates the impact on the reference values of simpler approaches using two quantifications methods, BRASS and Southampton, and explores the performance of the striatal phantom calibration in their harmonisation. RESULTS: BRASS and Southampton databases comprising 123 ENC-DAT subjects, from gamma cameras with parallel collimators, were reconstructed using filtered back projection (FBP) and iterative reconstruction OSEM without corrections (IRNC) and compared against the recommended OSEM with corrections for attenuation and scatter and septal penetration (ACSC), before and after applying phantom calibration. Differences between databases were quantified using the percentage difference of their SBR in the dopamine transporter-rich striatum, with their significance determined by the paired t test with Bonferroni correction. Attenuation and scatter losses, measured from the percentage difference between IRNC and ACSC databases, were of the order of 47% for both BRASS and Southampton quantifications. Phantom corrections were able to recover most of these losses, but the SBRs remained significantly lower than the "true" values (p < 0.001). Calibration provided, in fact, "first order" camera-dependent corrections, but could not include "second order" subject-dependent effects, such as septal penetration from extra-cranial activity. As for the ACSC databases, phantom calibration was instrumental in compensating for partial volume losses in BRASS (~67%, p < 0.001), while for the Southampton method, inherently free from them, it brought no significant changes and solely corrected for residual inter-camera variability (-0.2%, p = 0.44). CONCLUSIONS: The ENC-DAT reference values are significantly dependent on the reconstruction and quantification methods and phantom calibration, while reducing the major part of their differences, is unable to fully harmonize them. Clinical use of any normal database, therefore, requires consistency with the processing methodology. Caution must be exercised when comparing data from different centres, recognising that the SBR may represent an "index" rather than a "true" value.

The accuracy of quantitative parameters in (99m) Tc-MAG3 dynamic renography: a national audit based on virtual image data.

Assessment of image analysis methods and computer software used in (99m) Tc-MAG3 dynamic renography is important to ensure reliable study results and ultimately the best possible care for patients. In this work, we present a national multicentre study of the quantification accuracy in (99m) Tc-MAG3 renography, utilizing virtual dynamic scintigraphic data obtained by Monte Carlo-simulated scintillation camera imaging of digital phantoms with time-varying activity distributions. Three digital phantom studies were distributed to the participating departments, and quantitative evaluation was performed with standard clinical software according to local routines. The differential renal function (DRF) and time to maximum renal activity (Tmax ) were reported by 21 of the 28 Swedish departments performing (99m) Tc-MAG3 studies as of 2012. The reported DRF estimates showed a significantly lower precision for the phantom with impaired renal uptake than for the phantom with normal uptake. The Tmax estimates showed a similar trend, but the difference was only significant for the right kidney. There was a significant bias in the measured DRF for all phantoms caused by different positions of the left and right kidney in the anterior-posterior direction. In conclusion, this study shows that virtual scintigraphic studies are applicable for quality assurance and that there is a considerable uncertainty associated with standard quantitative parameters in dynamic (99m) Tc-MAG3 renography, especially for patients with impaired renal function.

Neurobiology of Sleep Disturbances in PTSD Patients and Traumatized Controls: MRI and SPECT Findings.

OBJECTIVE: Sleep disturbances such as insomnia and nightmares are core components of post-traumatic stress disorder (PTSD), yet their neurobiological relationship is still largely unknown. We investigated brain alterations related to sleep disturbances in PTSD patients and controls by using both structural and functional neuroimaging techniques. METHOD: Thirty-nine subjects either developing (n = 21) or not developing (n = 18) PTSD underwent magnetic resonance imaging and a symptom-provocation protocol followed by the injection of 99mTc-hexamethylpropyleneamineoxime. Subjects were also tested with diagnostic and self-rating scales on the basis of which a Sleep Disturbances Score (SDS; i.e., amount of insomnia/nightmares) was computed. RESULTS: Correlations between SDS and gray matter volume (GMV)/regional cerebral blood flow (rCBF) were computed in the whole sample and separately in the PTSD and control groups. In the whole sample, higher sleep disturbances were associated with significantly reduced GMV in amygdala, hippocampus, anterior cingulate, and insula; increased rCBF in midbrain, precuneus, and insula; and decreased rCBF in anterior cingulate. This pattern was substantially confirmed in the PTSD group, but not in controls. CONCLUSION: Sleep disturbances are associated with GMV loss in anterior limbic/paralimbic, PTSD-sensitive structures and with functional alterations in regions implicated in rapid eye movement-sleep control, supporting the existence of a link between PTSD and sleep disturbance.

Evaluation of inter-departmental variability of ejection fraction and cardiac volumes in myocardial perfusion scintigraphy using simulated data.

BACKGROUND: Myocardial perfusion scintigraphy (MPS) is a clinically useful noninvasive imaging modality for diagnosing patients with suspected coronary artery disease. By utilizing gated MPS, the end diastolic volume (EDV) and end systolic volume (ESV) can be measured and the ejection fraction (EF) calculated, which gives incremental prognostic value compared with assessment of perfusion only. The aim of this study was to evaluate the inter-departmental variability of EF, ESV, and EDV during gated MPS in Sweden. METHODS: Seventeen departments were included in the study. The SIMIND Monte Carlo (MC) program together with the XCAT phantom was used to simulate three patient cases with different EDV, ESV, and EF. Individual simulations were performed for each department, corresponding to their specific method of performing MPS. Images were then sent to each department and were evaluated according to clinical routine. EDV, ESV, and EF were reported back. RESULTS: There was a large underestimation of EDV and ESV for all three cases. Mean underestimation for EDV varied between 26% and 52% and for ESV between 15% and 60%. EF was more accurately measured, but mean bias still varied between an underestimation of 24% to an overestimation of 14%. In general, the intra-departmental variability for EDV, ESV, and EF was small, whereas inter-departmental variability was larger. CONCLUSIONS: Left ventricular volumes were generally underestimated, whereas EF was more accurately estimated. There was, however, large inter-departmental variability.

Using PET/CT Bone Scan Dynamic Data to Evaluate Tibia Remodeling When a Taylor Spatial Frame Is Used: Short and Longer Term Differences.

Eighteen consecutive patients, treated with a Taylor Spatial Frame for complex tibia conditions, gave their informed consent to undergo Na(18)F(-) PET/CT bone scans. We present a Patlak-like analysis utilizing an approximated blood time-activity curve eliminating the need for blood aliquots. Additionally, standardized uptake values (SUV) derived from dynamic acquisitions were compared to this Patlak-like approach. Spherical volumes of interest (VOIs) were drawn to include broken bone, other (normal) bone, and muscle. The SUV m (t) (m = max, mean) and a series of slopes were computed as (SUV m (t i ) - SUV m (t j ))/(t i - t j ), for pairs of time values t i and t j . A Patlak-like analysis was performed for the same time values by computing ((VOI p (t i )/VOI e (t i ))-(VOI p (t j )/VOI e (t j )))/(t i - t j ), where p = broken bone, other bone, and muscle and e = expected activity in a VOI. Paired comparisons between Patlak-like and SUV m slopes showed good agreement by both linear regression and correlation coefficient analysis (r = 84%, r s = 78%-SUVmax, r = 92%, and r s = 91%-SUVmean), suggesting static scans could substitute for dynamic studies. Patlak-like slope differences of 0.1 min(-1) or greater between examinations and SUVmax differences of ~5 usually indicated good remodeling progress, while negative Patlak-like slope differences of -0.06 min(-1) usually indicated poor remodeling progress in this cohort.

Reduced acquisition times in whole body bone scintigraphy using a noise-reducing Pixon®-algorithm-a qualitative evaluation study.

BACKGROUND: Reducing scan-time while maintaining sufficient image quality is a common issue in nuclear medicine diagnostics. This matter can be addressed by different post-processing methods such as Pixon® image processing. The aim of the present study was to evaluate if a commercially available noise-reducing Pixon-algorithm applied on whole body bone scintigraphy acquired with half the standard scan-time could provide the same clinical information as full scan-time non-processed images. METHODS: Twenty patients were administered with 500 MBq (99m)Tc-diphosphonate and scanned on a Siemens Symbia T16 system. Each patient was first imaged using a standard clinical protocol and subsequently imaged using a protocol with half the standard scan-time. Half-time images were processed using a commercially available software package, Enhanced Planar Processing, from Siemens. All images were anonymized and visually evaluated with regard to clinically relevant lesion detectability by three experienced nuclear medicine physicians. The result of this evaluation was grouped into four BMI intervals to investigate the performance of the algorithm with regard to different patient size. Also, a comparison study was performed where the physicians compared the standard image and the processed half-time image corresponding to the same patient with regard to lesion detectability, image noise, and artifacts. RESULTS: The results showed that 93 % of the processed half-time images and 98 % of the standard images were rated as sufficient or good with regard to lesion detectability. The processed half-time images were predominately considered sufficient (65 %), whereas the majority of the standard images were graded as good (83 %). The performance of the algorithm was unaffected by patient size as the average grading of all half-time processed images was constant independent of patient BMI. The comparison study showed that the standard images were rated superior with regard to lesion detectability, image noise, and artifacts, in 32, 65, and 23 % of the evaluations, respectively. CONCLUSIONS: The results indicate that the Pixon Enhanced Planar Processing does not fully compensate for the loss of counts associated with reducing the scan-time in half for whole body bone scintigraphies. The findings showed that implementing the Pixon-algorithm on images acquired with half the acquisition time in overall provide sufficient clinical information regardless of patient size. The half-time processed images were predominantly graded lower in comparison to images acquired with full time protocols, and a less aggressive reduction in scan-time is therefore recommended.

Towards mapping the brain connectome in depression: functional connectivity by perfusion SPECT.

Several studies have demonstrated altered brain functional connectivity in the resting state in depression. However, no study has investigated interregional networking in patients with persistent depressive disorder (PDD). The aim of this study was to assess differences in brain perfusion distribution and connectivity between large groups of patients and healthy controls. Participants comprised 91 patients with PDD and 65 age- and sex-matched healthy controls. Resting state perfusion was investigated by single photon emission computed tomography, and group differences were assessed by Statistical Parametric Mapping. Brain connectivity was explored through a voxel-wise interregional correlation analysis using as covariate of interest the normalized values of clusters of voxels in which perfusion differences were found in group analysis. Significantly increased regional brain perfusion distribution covering a large part of the cerebellum was observed in patients as compared with controls. Patients showed a significant negative functional connectivity between the cerebellar cluster and caudate, bilaterally. This study demonstrated inverse relative perfusion between the cerebellum and the caudate in PDD. Functional uncoupling may be associated with a dysregulation between the role of the cerebellum in action control and of the caudate in action selection, initiation and decision making in the patients. The potential impact of the resting state condition and the possibility of mitochondrial impairment are discussed.

(18)F-MCL-524, an (18)F-Labeled Dopamine D2 and D3 Receptor Agonist Sensitive to Dopamine: A Preliminary PET Study.

UNLABELLED: PET has been used to examine changes in neurotransmitter concentrations in the living brain. Pioneering PET studies on the dopamine system have used D2 and D3 receptor (D2/D3) antagonists such as (11)C-raclopride. However, more recently developed agonist radioligands have shown enhanced sensitivity to endogenous dopamine. A limitation of available agonist radioligands is that they incorporate the short-lived radioisotope (11)C. In the current study, we developed the (18)F-labeled D2/D3 receptor agonist (R)-(-)-2-(18)F-fluoroethoxy-N-n-propylnorapomorphine ((18)F-MCL-524). METHODS: In total, 10 PET measurements were conducted on 5 cynomolgus monkeys. Initially, the binding of (18)F-MCL-524 was compared with that of (11)C-MNPA in 3 monkeys. Second, the specificity of (18)F-MCL-524 binding was examined in pretreatment studies using raclopride (1.0 mg/kg) and d-amphetamine (1.0 mg/kg). Third, a preliminary kinetic analysis was performed using the radiometabolite-corrected arterial input function of the baseline studies. Finally, 2 whole-body PET measurements were conducted to evaluate biodistribution and radiation dosimetry after intravenous injection of (18)F-MCL-524. RESULTS: (18)F-MCL-524 entered the brain and provided striatum-to-cerebellum ratios suitable for reliable quantification of receptor binding using the multilinear reference tissue model. Mean striatal nondisplaceable binding potential (BPND) values were 2.0 after injection of (18)F-MCL-524 and 1.4 after (11)C-MNPA. The ratio of the BPND values of (18)F-MCL-524 and (11)C-MNPA was 1.5 across striatal subregions. After administration of raclopride and d-amphetamine, the (18)F-MCL-524 BPND values were reduced by 89% and 56%, respectively. Preliminary kinetic analysis demonstrated that BPND values obtained with the 1-tissue- and 2-tissue-compartment models were similar to values obtained with the multilinear reference tissue model. Estimated radiation doses were highest for gallbladder (0.27 mSv/MBq), upper large intestine (0.19 mSv/MBq), and small intestine (0.17 mSv/MBq). The estimated effective dose was 0.035 mSv/MBq. CONCLUSION: The (18)F-labeled agonist (18)F-MCL-524 appears suitable for quantification of D2/D3 receptor binding in vivo, and the results encourage extension to human studies. The longer half-life of (18)F makes (18)F-MCL-524 attractive for studies on modulation of the dopamine concentration-for example, in combination with simultaneous measurement of changes in blood-oxygen-level-dependent signal using bimodal PET/functional MRI.

Can Na18F PET/CT be used to study bone remodeling in the tibia when patients are being treated with a Taylor Spatial Frame?

Monitoring and quantifying bone remodeling are of interest, for example, in correction osteotomies, delayed fracture healing pseudarthrosis, bone lengthening, and other instances. Seven patients who had operations to attach an Ilizarov-derived Taylor Spatial Frame to the tibia gave informed consent. Each patient was examined by Na(18)F PET/CT twice, at approximately six weeks and three months after the operation. A validated software tool was used for the following processing steps. The first and second CT volumes were aligned in 3D and the respective PET volumes were aligned accordingly. In the first PET volume spherical volumes of interest (VOIs) were delineated for the crural fracture and normal bone and transferred to the second PET volume for SUVmax evaluation. This method potentially provides clinical insight into questions such as, when has the bone remodeling progressed well enough to safely remove the TSF? and when is intervention required, in a timelier manner than current methods? For example, in two patients who completed treatment, the SUVmax between the first and second PET/CT examination decreased by 42% and 13%, respectively. Further studies in a larger patient population are needed to verify these preliminary results by correlating regional Na(18)F PET measurements to clinical and radiological findings.