What is the added value of specialist radiology review of multidisciplinary team meeting cases in a tertiary care center?

PURPOSE: Multidisciplinary team meetings (MDTMs) are an important component of the workload of radiologists. This study investigated how often subspecialized radiologists change patient management in MDTMs at a tertiary care institution. MATERIALS AND METHODS: Over 2 years, six subspecialty radiologists documented their contributions to MDTMs at a tertiary care center. Both in-house and external imaging examinations were discussed at the MDTMs. All imaging examinations (whether primary or second opinion) were interpreted and reported by subspecialty radiologist prior to the MDTMs. The management change ratio (MCratio) of the radiologist was defined as the number of cases in which the radiologist's input in the MDTM changed patient management beyond the information that was already provided by the in-house (primary or second opinion) radiology report, as a proportion of the total number of cases whose imaging examinations were prepared for demonstration in the MDTM. RESULTS: Sixty-eight MDTMs were included. The time required for preparing and attending all MDTMs (excluding imaging examinations that had not been reported yet) was 11,000 min, with a median of 172 min (IQR 113-200 min) per MDTM, and a median of 9 min (IQR 8-13 min) per patient. The radiologists' input changed patient management in 113 out of 1138 cases, corresponding to an MCratio of 8.4%. The median MCratio per MDTM was 6% (IQR 0-17%). CONCLUSION: Radiologists' time investment in MDTMs is considerable relative to the small proportion of cases in which they influence patient management in the MDTM. The use of radiologists for MDTMs should therefore be improved. CLINICAL RELEVANCE STATEMENT: The use of radiologists for MDTMs (multidisciplinary team meetings) should be improved, because their time investment in MDTMs is considerable relative to the small proportion of cases in which they influence patient management in the MDTM. KEY POINTS: • Multidisciplinary team meetings (MDTMs) are an important component of the workload of radiologists. • In a tertiary care center in which all imaging examinations have already been interpreted and reported by subspecialized radiologists before the MDTM takes place, the median time investment of a radiologist for preparing and demonstrating one MDTM patient is 9 min. • In this setting, the radiologist changes patient management in only a minority of cases in the MDTM.

Focused view CT angiography for selective visualization of stroke related arteries: technical feasibility.

OBJECTIVES: This study investigated the technical feasibility of focused view CTA for the selective visualization of stroke related arteries. METHODS: A total of 141 CTA examinations for acute ischemic stroke evaluation were divided into a set of 100 cases to train a deep learning algorithm (dubbed "focused view CTA") that selectively extracts brain (including intracranial arteries) and extracranial arteries, and a test set of 41 cases. The visibility of anatomic structures at focused view and unmodified CTA was assessed using the following scoring system: 5 = completely visible, diagnostically sufficient; 4 = nearly completely visible, diagnostically sufficient; 3 = incompletely visible, barely diagnostically sufficient; 2 = hardly visible, diagnostically insufficient; 1 = not visible, diagnostically insufficient. RESULTS: At focused view CTA, median scores for the aortic arch, subclavian arteries, common carotid arteries, C1, C6, and C7 segments of the internal carotid arteries, V4 segment of the vertebral arteries, basilar artery, cerebellum including cerebellar arteries, cerebrum including cerebral arteries, and dural venous sinuses, were all 4. Median scores for the C2 to C5 segments of the internal carotid arteries, and V1 to V3 segments of the vertebral arteries ranged between 3 and 2. At unmodified CTA, median score for all above-mentioned anatomic structures was 5, which was significantly higher (p < 0.0001) than that at focused view CTA. CONCLUSION: Focused view CTA shows promise for the selective visualization of stroke-related arteries. Further improvements should focus on more accurately visualizing the smaller and tortuous internal carotid and vertebral artery segments close to bone. CLINICAL RELEVANCE: Focused view CTA may speed up image interpretation time for LVO detection and may potentially be used as a tool to study the clinical relevance of incidental findings in future prospective long-term follow-up studies. KEY POINTS: • A deep learning-based algorithm ("focused view CTA") was developed to selectively visualize relevant structures for acute ischemic stroke evaluation at CTA. • The elimination of unrequested anatomic background information was complete in all cases. • Focused view CTA may be used to study the clinical relevance of incidental findings.

Amyloid imaging of dutch-type hereditary cerebral amyloid angiopathy carriers.

OBJECTIVE: To determine whether amyloid imaging with the positron emission tomography (PET) agent Pittsburgh compound B (PiB) can detect vascular ß-amyloid (Aß) in the essentially pure form of cerebral amyloid angiopathy associated with the Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) mutation. METHODS: PiB retention in a cortical composite of frontal, lateral, and retrosplenial regions (FLR) was measured by PiB-PET in 19 D-CAA mutation carriers (M+ ; 13 without neurologic symptoms, 6 with prior lobar intracerebral hemorrhage) and 17 mutation noncarriers (M- ). Progression of PiB retention was analyzed in a subset of 18 serially imaged individuals (10 asymptomatic M+ , 8 M- ). We also analyzed associations between PiB retention and cerebrospinal fluid (CSF) Aß concentrations in 17 M+ and 11 M- participants who underwent lumbar puncture and compared the findings to PiB-PET and CSF Aß in 37 autosomal dominant Alzheimer disease (ADAD) mutation carriers. RESULTS: D-CAA M+ showed greater age-dependent FLR PiB retention (p < 0.001) than M- , and serially imaged asymptomatic M+ demonstrated greater longitudinal increases (p = 0.004). Among M+ , greater FLR PiB retention associated with reduced CSF concentrations of Aß40 (r = -0.55, p = 0.021) but not Aß42 (r = 0.01, p = 0.991). Despite comparably low CSF Aß40 and Aß42, PiB retention was substantially less in D-CAA than ADAD (p < 0.001). INTERPRETATION: Increased PiB retention in D-CAA and correlation with reduced CSF Aß40 suggest this compound labels vascular amyloid, although to a lesser degree than amyloid deposits in ADAD. Progression in PiB signal over time suggests amyloid PET as a potential biomarker in trials of candidate agents for this untreatable cause of hemorrhagic stroke. ANN NEUROL 2019;86:616-625.

Macrophage positron emission tomography imaging as a biomarker for preclinical rheumatoid arthritis: findings of a prospective pilot study.

OBJECTIVE: To conduct a prospective pilot study to determine whether macrophage targeting by 11C-(R)-PK11195 positron emission tomography (PET) can visualize subclinical synovitis in arthralgia patients who have anti-citrullinated protein antibodies (ACPAs). METHODS: Twenty-nine arthralgia patients who were positive for ACPAs but did not have clinical arthritis were studied. High (spatial)-resolution 11C-(R)-PK11195 PET scans of the hands and wrists were performed. For all metacarpophalangeal, proximal interphalangeal, and wrist joints (i.e., 22 joints per patient), tracer uptake was scored semiquantitatively (0-3 scale) by 2 observers who were blinded with regard to the clinical data. Patients were followed up prospectively for 24 months to investigate the development of clinical arthritis. RESULTS: Overall agreement and kappa values for the readings of the 2 observers were, respectively, 97% and 0.91 (95% confidence interval [95% CI] 0.74-1) at the patient level and 99% and 0.81 (95% CI 0.65-0.96) at the joint level. In 4 patients, at least 1 and as many as 5 PET-positive joints (score≥1) were found at baseline. Within 2 years of followup, 9 patients had developed clinical arthritis. This included all 4 patients with positive findings on the 11C-(R)-PK11195 scan, who developed clinical arthritis in the hand/wrist region, as identified on PET scans. Of the 5 remaining arthritis patients with negative findings on PET scans, 2 developed arthritis in the hand joints and 3 developed arthritis at locations outside the field of view of the PET scanner. CONCLUSION: Subclinical arthritis in ACPA-positive arthralgia patients could be visualized by 11C-(R)-PK11195 PET scanning and was associated with development of arthritis within 2 years of followup. This indicates that 11C-(R)-PK11195 PET may be useful in determining arthritis activity in the preclinical phase of RA.

Amyloid burden and metabolic function in early-onset Alzheimer's disease: parietal lobe involvement.

Alzheimer's disease with early onset often presents with a distinct cognitive profile, potentially reflecting a different distribution of underlying neuropathology. The purpose of this study was to examine the relationships between age and both in vivo fibrillary amyloid deposition and glucose metabolism in patients with Alzheimer's disease. Dynamic [(11)C]Pittsburgh compound-B (90 min) and static [(18)F]fluorodeoxyglucose (15 min) scans were obtained in 100 patients with Alzheimer's disease and 20 healthy controls. Parametric non-displaceable binding potential images of [(11)C]Pittsburgh compound-B and standardized uptake value ratio images of [(18)F]fluorodeoxyglucose were generated using cerebellar grey matter as reference tissue. Nine [(11)C]Pittsburgh compound-B-negative patients were excluded. The remaining patients were categorized into younger (n=45, age: 56 ± 4 years) and older (n=46, age: 69 ± 5 years) groups, based on the median age (62 years) at time of diagnosis. Younger patients showed more severe impairment on visuo-spatial function, attention and executive function composite scores (P<0.05), while we found a trend towards poorer memory performance for older patients (P=0.11). Differences between groups were assessed using a general linear model with repeated measures (gender adjusted) with age as between subjects factor, region (frontal, temporal, parietal and occipital and posterior cingulate cortices) as within subjects factor and [(11)C]Pittsburgh compound-B binding/[(18)F]fluorodeoxyglucose uptake as dependent variables. There was no main effect of age for [(11)C]Pittsburgh compound-B or [(18)F]fluorodeoxyglucose, suggesting that overall, the extent of amyloid deposition or glucose hypometabolism did not differ between groups. Regional distributions of [(11)C]Pittsburgh compound-B binding and [(18)F]fluorodeoxyglucose uptake (both P for interaction <0.05) differed between groups, however, largely due to increased [(11)C]Pittsburgh compound-B binding and decreased [(18)F]fluorodeoxyglucose uptake in the parietal cortex of younger patients (both P<0.05). Linear regression analyses showed negative associations between visuo-spatial functioning and parietal [(11)C]Pittsburgh compound-B binding for younger patients (standardized ß: -0.37) and between visuo-spatial functioning and occipital binding for older patients (standardized ß: -0.39). For [(18)F]fluorodeoxyglucose, associations were found between parietal uptake with visuo-spatial (standardized ß: 0.55), attention (standardized ß: 0.39) and executive functioning (standardized ß: 0.37) in younger patients, and between posterior cingulate uptake and memory in older patients (standardized ß: 0.41, all P<0.05). These in vivo findings suggest that clinical differences between younger and older patients with Alzheimer's disease are not restricted to topographical differentiation in downstream processes but may originate from distinctive distributions of early upstream events. As such, increased amyloid burden, together with metabolic dysfunction, in the parietal lobe of younger patients with Alzheimer's disease may contribute to the distinct cognitive profile in these patients.

Susceptibility-weighted imaging in intracranial hemorrhage: not all bleeds are black.

To correctly recognize intracranial hemorrhage (ICH) and differentiate it from other lesions, knowledge of the imaging characteristics of an ICH on susceptibility weighted imaging (SWI) is essential. It is a common misconception that blood is always black on SWI, and it is important to realize that hemorrhage has a variable appearance in different stages on SWI. Furthermore, the presence of a low signal on SWI does not equal the presence of blood products. In this review, the appearance of ICH on SWI during all its stages and common other causes of a low signal on SWI are further discussed and illustrated.

Measuring response to therapy using FDG PET: semi-quantitative and full kinetic analysis.

PURPOSE: Imaging with positron emission tomography (PET) using (18)F-2-fluoro-2-deoxy-D: -glucose (FDG) plays an increasingly important role for response assessment in oncology. Several methods for quantifying FDG PET results exist. The goal of this study was to analyse and compare various semi-quantitative measures for response assessment with full kinetic analysis, specifically in assessment of novel therapies. METHODS: Baseline and response dynamic FDG studies from two different longitudinal studies (study A: seven subjects with lung cancer and study B: six subjects with gastrointestinal cancer) with targeted therapies were reviewed. Quantification of tumour uptake included full kinetic methods, i.e. nonlinear regression (NLR) and Patlak analyses, and simplified measures such as the simplified kinetic method (SKM) and standardized uptake value (SUV). An image-derived input function was used for NLR and Patlak analysis. RESULTS: There were 18 and 9 lesions defined for two response monitoring studies (A and B). In all cases there was excellent correlation between Patlak- and NLR-derived response (R (2) > 0.96). Percentage changes seen with SUV were significantly different from those seen with Patlak for both studies (p < 0.05). After correcting SUV for plasma glucose, SUV and Patlak responses became similar for study A, but large differences remained for study B. Further analysis revealed that differences in responses amongst methods in study B were primarily due to changes in the arterial input functions. CONCLUSION: Use of simplified methods for assessment of drug efficacy or treatment response may provide different results than those seen with full kinetic analysis.

Primary Cauda Equina T-Cell Lymphoblastic Lymphoma.

BACKGROUND: T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive form of non-Hodgkin lymphoma. This report describes, to our knowledge, the first adult case of a primary cauda equina T-LBL. Treatment consists of multiagent chemotherapy, and surgical removal of T-LBL does not improve outcome. We discuss the workup of patients with an intradural spinal mass, together with a review of the literature on primary spinal lymphoma of the cauda equina. CASE DESCRIPTION: A 54-year-old woman with Crohn's disease, for which she was taking immunosuppressive medication, presented with progressive back pain radiating to both legs and deteriorating neurologic deficits caused by an intradural, contrast-enhancing lesion in the L1-5 region. During acute surgery, the tumor was partially resected. Immunohistochemical phenotyping revealed a T-LBL. No other lymphoma localizations were found after subsequent staging. Despite extensive treatment, the patient died of disseminated disease throughout the central nervous system, 6 weeks after the diagnosis. CONCLUSIONS: Pain and progressive neurologic complaints can be symptoms of a (malignant) intradural spinal tumor. Intradural lymphoma must be considered as a differential diagnosis by clinicians because it can mimic neoplasms that often require urgent surgery. The histopathologic diagnosis should preferably be obtained by way of cerebrospinal fluid analysis or tumor biopsy because tumor resection has no beneficial effect on the oncologic outcome.

Accuracy of 3-dimensional reconstruction algorithms for the high-resolution research tomograph.

UNLABELLED: The high-resolution research tomograph (HRRT) is a dedicated human brain PET scanner. At present, iterative reconstruction methods are preferred for reconstructing HRRT studies. However, these iterative reconstruction algorithms show bias in short-duration frames. New algorithms such as the shifted Poisson ordered-subsets expectation maximization (SP-OSEM) and ordered-subsets weighted least squares (OSWLS) showed promising results in bias reduction, compared with the recommended ordinary Poisson OSEM (OP-OSEM). The goal of this study was to evaluate quantitative accuracy of these iterative reconstruction algorithms, compared with 3-dimensional filtered backprojection (3D-FBP). METHODS: The 3 above-mentioned 3D iterative reconstruction methods were implemented for the HRRT. To evaluate the various 3D iterative reconstruction techniques quantitatively, several phantom studies and a human brain study (n=5) were performed. RESULTS: OSWLS showed a low and almost linearly increasing coefficient of variation (SD over average activity concentration), with decreasing noise-equivalent count rates. In decay studies, OSWLS showed good agreement with the 3D-FBP gray matter (GM)-to-white matter (WM) contrast ratio (<4%), and OP-OSEM and SP-OSEM showed agreement within 6% and 7%, respectively. For various frame durations, both SP-OSEM and OP-OSEM showed the fewest errors in GM-to-WM contrast ratios, varying 75% between different noise-equivalent count rates; this variability was much higher for other iterative methods (>92%). 3D-FBP showed the least variability (34%). Visually, OSWLS hardly showed any artifacts in parametric images and showed good agreement with 3D-FBP data for parametric images, especially in the case of reference-tissue kinetic methods (slope, 1.02; Pearson correlation coefficient, 0.99). CONCLUSION: OP-OSEM, SP-OSEM, and OSWLS showed good performance for phantom studies. In addition, OSWLS showed better results for parametric analysis of clinical studies and is therefore recommended for quantitative HRRT brain PET studies.

HRRT versus HR+ human brain PET studies: an interscanner test-retest study.

UNLABELLED: The high-resolution research tomograph (HRRT) is a dedicated human brain PET scanner. The purpose of this study was to compare the quantitative accuracy of the HRRT with that of the clinical HR+ PET scanner and to assess effects of differences in spatial resolution between both scanners ( approximately 2.7 mm and approximately 7.0 mm for HRRT and HR+, respectively). METHODS: Paired (11)C-flumazenil scans of 7 healthy volunteers were assessed. For each volunteer, dynamic scans (including arterial sampling) were acquired on both scanners on the same day, thereby minimizing intersubject variability. Volume of distribution was generated using Logan plot analysis with plasma input. In addition, other plasma input, reference tissue (with pons as the reference tissue input), and parametric methods were included in the interscanner comparison. RESULTS: Logan volume-of-distribution analysis of HRRT data showed higher values than that of HR+ data (slope with the intercept fixed at the origin of 1.14 +/- 0.10 to 1.19 +/- 0.10, depending on the HRRT reconstruction method used). Smoothing HRRT reconstructions with a 6-mm full width at half maximum gaussian kernel reduced this slope toward the line of identity (1.04 +/- 0.11 to 1.07 +/- 0.11), retaining good correlation between HR+ and HRRT data (r, approximately 0.98). Similar trends were observed for other plasma input, reference tissue, and parametric methods. However, after reference matching the reference tissue models showed lower HRRT kinetic parameter values than HR+ values (slope with fixed intercept, 0.90 +/- 0.10 to 0.94 +/- 0.13). CONCLUSION: Higher values of pharmacokinetic parameter values, obtained from HRRT versus HR+ PET studies, indicate improved HRRT PET quantification primarily due to a reduction in partial-volume effects.

(124)I-L19-SIP for immuno-PET imaging of tumour vasculature and guidance of (131)I-L19-SIP radioimmunotherapy.

PURPOSE: The human monoclonal antibody (MAb) fragment L19-SIP is directed against extra domain B (ED-B) of fibronectin, a marker of tumour angiogenesis. A clinical radioimmunotherapy (RIT) trial with (131)I-L19-SIP was recently started. In the present study, after GMP production of (124)I and efficient production of (124)I-L19-SIP, we aimed to demonstrate the suitability of (124)I-L19-SIP immuno-PET for imaging of angiogenesis at early-stage tumour development and as a scouting procedure prior to clinical (131)I-L19-SIP RIT. METHODS: (124)I was produced in a GMP compliant way via (124)Te(p,n)(124)I reaction and using a TERIMO module for radioiodine separation. L19-SIP was radioiodinated by using a modified version of the IODO-GEN method. The biodistribution of coinjected (124)I- and (131)I-L19-SIP was compared in FaDu xenograft-bearing nude mice, while (124)I PET images were obtained from mice with tumours of <50 to approximately 700 mm(3). RESULTS: (124)I was produced highly pure with an average yield of 15.4 +/- 0.5 MBq/microAh, while separation yield was approximately 90% efficient with <0.5% loss of TeO(2). Overall labelling efficiency, radiochemical purity and immunoreactive fraction were for (124)I-L19-SIP: approximately 80 , 99.9 and >90%, respectively. Tumour uptake was 7.3 +/- 2.1, 10.8 +/- 1.5, 7.8 +/- 1.4, 5.3 +/- 0.6 and 3.1 +/- 0.4%ID/g at 3, 6, 24, 48 and 72 h p.i., resulting in increased tumour to blood ratios ranging from 6.0 at 24 h to 45.9 at 72 h p.i.. Fully concordant labelling and biodistribution results were obtained with (124)I- and (131)I-L19-SIP. Immuno-PET with (124)I-L19-SIP using a high-resolution research tomograph PET scanner revealed clear delineation of the tumours as small as 50 mm(3) and no adverse uptake in other organs. CONCLUSIONS: (124)I-MAb conjugates for clinical immuno-PET can be efficiently produced. Immuno-PET with (124)I-L19-SIP appeared qualified for sensitive imaging of tumour neovasculature and for predicting (131)I-L19-SIP biodistribution.

No signs of metabolic hyperactivity in patients with unilateral condylar hyperactivity: an in vivo positron emission tomography study.

PURPOSE: The purpose of this study was to assess bone growth and blood flow in the condylar region in patients with unilateral condylar hyperactivity (UCH) by use of positron emission tomography (PET). PATIENTS AND METHODS: This prospective study included 7 patients with UCH and a control group of 6 volunteers. In addition to normal clinical investigations, labeled fluoride ((18)F(-)) and oxygen 15-labeled water (H(2)(15)O) PET scans were performed. RESULTS: In control subjects the net rate of fluoride influx, representing bone metabolism, was similar for left and right condylar sides. Interestingly, this was not significantly different from the affected condyles in UCH patients. Rather, the net rate of fluoride influx on the contralateral side of UCH patients was reduced significantly compared with the affected side (P= .02) and control subjects (P= .004). The mean blood flow on the left and right condylar sides in control subjects was not significantly different. The same was true for the hyperactive and contralateral condyles of UCH patients. Blood flow in the condylar region in UCH patients was similar to that in the control group. CONCLUSIONS: There was no evidence of an abnormally high rate of bone growth in the affected condylar region in UCH patients. Instead, the rate of bone growth appeared to be reduced in the contralateral condylar region. These PET results are in contrast to the characteristic clinical picture of UCH patients and suggest the possibility of subgroups in patients with a mandibular asymmetry caused by UCH. Furthermore, no evidence of hypervascularization of the condylar region in UCH patients was found.

Image derived input functions for dynamic High Resolution Research Tomograph PET brain studies.

The High Resolution Research Tomograph (HRRT) is a dedicated human brain positron emission tomography (PET) scanner. The aim of the present study was to validate the use of image derived input functions (IDIF) as an alternative for arterial sampling for HRRT human brain studies. To this end, IDIFs were extracted from 3D ordinary Poisson ordered subsets expectation maximization (OP-OSEM) and reconstruction based partial volume corrected (PVC) OP-OSEM images. IDIFs, either derived directly from regions of interest or further calibrated using manual samples taken during scans, were evaluated for dynamic [(11)C]flumazenil data (n=6). Results obtained with IDIFs were compared with those obtained using blood sampler input functions (BSIF). These comparisons included areas under the curve (AUC) for peak (0-3.3 min) and tail (3.3-55.0 min). In addition, slope, intercept and Pearson's correlation coefficient of tracer kinetic analysis results based on IDIF and BSIF were calculated for each subject. Good peak AUC ratios (0.83+/-0.21) between IDIF and BSIF were found for calibrated IDIFs extracted from OP-OSEM images. This combination of IDIFs and images also provided good slope values (1.07+/-0.11). Improved resolution, as obtained with PVC OP-OSEM, changed AUC ratios to 1.14+/-0.35 and, for tracer kinetic analysis, slopes changed to 0.95+/-0.13. For all reconstructions, non-calibrated IDIFs gave poorer results (>61+/-34% higher slopes) compared with calibrated IDIFs. The results of this study indicate that the use of IDIFs, extracted from OP-OSEM or PVC OP-OSEM images, is feasible for dynamic HRRT data, thereby obviating the need for online arterial sampling.

Impact of attenuation correction strategies on the quantification of High Resolution Research Tomograph PET studies.

In this study, the quantitative accuracy of different attenuation correction strategies presently available for the High Resolution Research Tomograph (HRRT) was investigated. These attenuation correction methods differ in reconstruction and processing (segmentation) algorithms used for generating a micro-image from measured 2D transmission scans, an intermediate step in the generation of 3D attenuation correction factors. Available methods are maximum-a-posteriori reconstruction (MAP-TR), unweighted OSEM (UW-OSEM) and NEC-TR, which transforms sinogram values back to their noise equivalent counts (NEC) to restore Poisson distribution. All methods can be applied with or without micro-image segmentation. However, for MAP-TR a micro-histogram is a prior during reconstruction. All possible strategies were evaluated using phantoms of various sizes, simulating preclinical and clinical situations. Furthermore, effects of emission contamination of the transmission scan on the accuracy of various attenuation correction strategies were studied. Finally, the accuracy of various attenuation corrections strategies and its relative impact on the reconstructed activity concentration (AC) were evaluated using small animal and human brain studies. For small structures, MAP-TR with human brain priors showed smaller differences in micro-values for transmission scans with and without emission contamination (<8%) than the other methods (<26%). In addition, it showed best agreement with true AC (deviation <4.5%). A specific prior designed to take into account the presence of small animal fixation devices only very slightly improved AC precision to 4.3%. All methods scaled micro-values of a large homogeneous phantom to within 4% of the water peak, but MAP-TR provided most accurate AC after reconstruction. However, for clinical data MAP-TR using the default prior settings overestimated the thickness of the skull, resulting in overestimations of micro-values in regions near the skull and thus in incorrect AC for cortical regions. Using NEC-TR with segmentation or MAP-TR with an adjusted human brain prior showed less overestimation in both skull thickness and AC for these structures and are therefore the recommended methods for human brain studies.

Comparison of 3D-OP-OSEM and 3D-FBP reconstruction algorithms for High-Resolution Research Tomograph studies: effects of randoms estimation methods.

The High-Resolution Research Tomograph (HRRT) is a dedicated human brain positron emission tomography (PET) scanner. Recently, a 3D filtered backprojection (3D-FBP) reconstruction method has been implemented to reduce bias in short duration frames, currently observed in 3D ordinary Poisson OSEM (3D-OP-OSEM) reconstructions. Further improvements might be expected using a new method of variance reduction on randoms (VRR) based on coincidence histograms instead of using the delayed window technique (DW) to estimate randoms. The goal of this study was to evaluate VRR in combination with 3D-OP-OSEM and 3D-FBP reconstruction techniques. To this end, several phantom studies and a human brain study were performed. For most phantom studies, 3D-OP-OSEM showed higher accuracy of observed activity concentrations with VRR than with DW. However, both positive and negative deviations in reconstructed activity concentrations and large biases of grey to white matter contrast ratio (up to 88%) were still observed as a function of scan statistics. Moreover 3D-OP-OSEM+VRR also showed bias up to 64% in clinical data, i.e. in some pharmacokinetic parameters as compared with those obtained with 3D-FBP+VRR. In the case of 3D-FBP, VRR showed similar results as DW for both phantom and clinical data, except that VRR showed a better standard deviation of 6-10%. Therefore, VRR should be used to correct for randoms in HRRT PET studies.

Evaluation of methods for generating parametric (R-[11C]PK11195 binding images.

Activated microglia can be visualised using (R)-[(11)C]PK11195 (1-[2-chlorophenyl]-N-methyl-N-[1-methyl-propyl]-3-isoquinoline carboxamide) and positron emission tomography (PET). In previous studies, various methods have been used to quantify (R)-[(11)C]PK11195 binding. The purpose of this study was to determine which parametric method would be best suited for quantifying (R)-[(11)C]PK11195 binding at the voxel level. Dynamic (R)-[(11)C]PK11195 scans with arterial blood sampling were performed in 20 healthy and 9 Alzheimer's disease subjects. Parametric images of both volume of distribution (V(d)) and binding potential (BP) were obtained using Logan graphical analysis with plasma input. In addition, BP images were generated using two versions of the basis function implementation of the simplified reference tissue model, two versions of Ichise linearisations, and Logan graphical analysis with reference tissue input. Results of the parametric methods were compared with results of full compartmental analysis using nonlinear regression. Simulations were performed to assess accuracy and precision of each method. It was concluded that Logan graphical analysis with arterial input function is an accurate method for generating parametric images of V(d). Basis function methods, one of the Ichise linearisations and Logan graphical analysis with reference tissue input provided reasonably accurate and precise estimates of BP. In pathological conditions with reduced flow rates or large variations in blood volume, the basis function method is preferred because it produces less bias and is more precise.

Evaluation of reference regions for (R)-[(11)C]PK11195 studies in Alzheimer's disease and mild cognitive impairment.

Inflammation in Alzheimer's disease (AD) may be assessed using (R)-[(11)C]PK11195 and positron emission tomography. Data can be analyzed using the simplified reference tissue model, provided a suitable reference region is available. This study evaluates various reference regions for analyzing (R)-[(11)C]PK11195 scans in patients with mild cognitive impairment (MCI) and probable AD. Healthy subjects (n=10, 30+/-10 years and n=10, 70+/-6 years) and patients with MCI (n=10, 74+/-6 years) and probable AD (n=9, 71+/-6 years) were included. Subjects underwent a dynamic three-dimensional (R)-[(11)C]PK11195 scan including arterial sampling. Gray matter, white matter, total cerebellum and cerebrum, and cluster analysis were evaluated as reference regions. Both plasma input binding potentials of these reference regions (BP(PLASMA)) and corresponding reference region input binding potentials of a target region (BP(SRTM)) were evaluated. Simulations were performed to assess cluster analysis performance at 5% to 15% coefficient of variation noise levels. Reasonable correlations for BP(PLASMA) (R(2)=0.52 to 0.94) and BP(SRTM) (R(2)=0.59 to 0.76) were observed between results using anatomic regions and cluster analysis. For cerebellum white matter, cerebrum white matter, and total cerebrum a considerable number of unrealistic BP(SRTM) values were observed. Cluster analysis did not extract a valid reference region in 10% of the scans. Simulations showed that potentially cluster analysis suffers from negative bias in BP(PLASMA). Most anatomic regions outperformed cluster analysis in terms of absence of both scan rejection and bias. Total cerebellum is the optimal reference region in this patient category.

Performance evaluation of the ECAT HRRT: an LSO-LYSO double layer high resolution, high sensitivity scanner.

The ECAT high resolution research tomograph (HRRT) is a dedicated brain and small animal PET scanner, with design features that enable high image spatial resolution combined with high sensitivity. The HRRT is the first commercially available scanner that utilizes a double layer of LSO/LYSO crystals to achieve photon detection with depth-of-interaction information. In this study, the performance of the commercial LSO/LYSO HRRT was characterized, using the NEMA protocol as a guideline. Besides measurement of spatial resolution, energy resolution, sensitivity, scatter fraction, count rate performance, correction for attenuation and scatter, hot spot recovery and image quality, a clinical evaluation was performed by means of a HR+/HRRT human brain comparison study. Point source resolution varied across the field of view from approximately 2.3 to 3.2 mm (FWHM) in the transaxial direction and from 2.5 to 3.4 mm in the axial direction. Absolute line-source sensitivity ranged from 2.5 to 3.3% and the NEMA-2001 scatter fraction equalled 45%. Maximum NECR was 45 kcps and 148 kcps according to the NEMA-2001 and 1994 protocols, respectively. Attenuation and scatter correction led to a volume uniformity of 6.3% and a system uniformity of 3.1%. Reconstructed values deviated up to 15 and 8% in regions with high and low densities, respectively, which can possibly be assigned to inaccuracies in scatter estimation. Hot spot recovery ranged from 60 to 94% for spheres with diameters of 1 to 2.2 cm. A high quantitative agreement was met between HR+ and HRRT clinical data. In conclusion, the ECAT HRRT has excellent resolution and sensitivity properties, which is a crucial advantage in many research studies.

Neurophysiological effects of sleep deprivation in healthy adults, a pilot study.

Total sleep deprivation (TSD) may induce fatigue, neurocognitive slowing and mood changes, which are partly compensated by stress regulating brain systems, resulting in altered dopamine and cortisol levels in order to stay awake if needed. These systems, however, have never been studied in concert. At baseline, after a regular night of sleep, and the next morning after TSD, 12 healthy subjects performed a semantic affective classification functional magnetic resonance imaging (fMRI) task, followed by a [11C]raclopride positron emission tomography (PET) scan. Saliva cortisol levels were acquired at 7 time points during both days. Affective symptoms were measured using Beck Depression Inventory (BDI), Spielberger State Trait Anxiety Index (STAI) and visual analogue scales. After TSD, perceived energy levels, concentration, and speed of thought decreased significantly, whereas mood did not. During fMRI, response speed decreased for neutral words and positive targets, and accuracy decreased trendwise for neutral words and for positive targets with a negative distracter. Following TSD, processing of positive words was associated with increased left dorsolateral prefrontal activation. Processing of emotional words in general was associated with increased insular activity, whereas contrasting positive vs. negative words showed subthreshold increased activation in the (para)hippocampal area. Cortisol secretion was significantly lower after TSD. Decreased voxel-by-voxel [11C]raclopride binding potential (BPND) was observed in left caudate. TSD induces widespread cognitive, neurophysiologic and endocrine changes in healthy adults, characterized by reduced cognitive functioning, despite increased regional brain activity. The blunted HPA-axis response together with altered [11C]raclopride binding in the basal ganglia indicate that sustained wakefulness requires involvement of additional adaptive biological systems.

Comparison of simplified parametric methods for visual interpretation of 11C-Pittsburgh compound-B PET images.

UNLABELLED: This study compared several parametric imaging methods to determine the optimal approach for visual assessment of parametric Pittsburgh compound-B ((11)C-PIB) PET images to detect cortical amyloid deposition in different memory clinic patient groups. METHODS: Dynamic (11)C-PIB scanning of 120 memory clinic patients was performed. Parametric nondisplaceable binding potential (BPND) images were compared with standardized uptake value (SUV) and SUV ratio images. Images were visually assessed by 3 independent readers, and both interreader and intermethod agreement was determined. RESULTS: Both 90-min (Fleiss κ = 0.88) and 60-min (Fleiss κ = 0.89) BPND images showed excellent interreader agreement, whereas agreement was good to moderate for SUV ratio images (Fleiss κ = 0.68) and SUV images (Fleiss κ = 0.59). Intermethod agreement varied substantially between readers, although BPND images consistently showed the best performance. CONCLUSION: The use of BPND images provided the highest interreader and intermethod agreement and is therefore the method of choice for optimal visual interpretation of (11)C-PIB PET scans.