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This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London Background: Modernisation of education encompasses the integration of technological advances, and more active participation of students in their learning through recognised, effective techniques such as Student Centred Learning (SCL). To increase active participation of students with their learning within a classroom environment, significant effort has focused on the integration of digital games into education. These techniques, known collectively as Digital Game-Based Learning (DGBL), show strong potential as a vehicle to deliver SCL, a method termed Student Centred Digital Game-Based Learning (SCDGBL). However, SCDGBL offerings have so far not been focused on the delivery of a fully student centred experience through a comprehensive integration of all seven tenets that comprise SCL. Aim: To design, develop and evaluate a novel DGBL experience that fully realises all seven tenets of SCL in delivering an engaging and effective educational experience. Methods: A design science research approach was used: A systematic literature review assessed state of the art, creating a conceptual framework for SCDGBL literature evaluation. A game design framework, the Student Centred Experience framework, was developed using design thinking and utilised to design a game-based educational artefact: the LogicGate System. It was deployed in a classroom environment to create a SCDGBL experience, with mixed methods evaluation blending user surveys and qualitative focus groups. The revised system, LogicGate-R, was evaluated against a traditional student-centred learning task for delivery of SCL tenets and learning outcomes producing knowledge improvement, by randomised cross-over trial design using a knowledge test, user surveys and qualitative focus group data on student experience. Results: The literature review demonstrated SCDGBL offerings do not currently deliver all seven SCL tenets, particularly the social aspects. In Experiment 1, students responded positively to the LogicGate System, feeling it was an engaging and effective way to learn, and made recommendations for improvements to immersion and feedback which were integrated into developing the high fidelity LogicGate-R System. A randomised cross-over trial, evaluating the Logic-Gate-R system, found that all SCL tenets were delivered while providing equivalent knowledge improvement to a traditional student-centred task. It was rated highly over the traditional task by students in feedback, joint productive activity and autonomy areas. Conclusions: The key contributions of this work include a conceptual framework to evaluate SCDGBL research, identifying gaps for redress. A highly customisable game design framework facilitates full delivery of SCL tenets and desired learning outcomes within a high quality game design. A game designed using this framework was demonstrated to deliver on all SCL tenets, including social aspects neglected in previous offerings. This enabled development of implications and recommendations for future design, usage and evaluation of SCDGBL offerings in educational settings.

The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer’s Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes. In this work, we present a combined framework, cascaded multiview canonical correlation (CaMCCo), for fusion and cascaded classification that incorporates all diagnostic categories and optimizes classification by selectively combining a subset of modalities at each level of the cascade. CaMCCo is evaluated on a data cohort comprising 149 patients for whom neurophysiological, neuroimaging, proteomic and genomic data were available. Results suggest that fusion of select modalities for each classification task outperforms (mean AUC = 0.92) fusion of all modalities (mean AUC = 0.54) and individual modalities (mean AUC = 0.90, 0.53, 0.71, 0.73, 0.62, 0.68). In addition, CaMCCo outperforms all other multi-class classification methods for MCI prediction (PPV: 0.80 vs. 0.67, 0.63).

On 3 March 1193, in the episcopal palace of Piacenza, in the presence of the bishop of Piacenza and a papal legate (Cardinal Peter of S. Cecilia), Gandolfo, abbot of the Piacentine monastery of S. Sisto, presented a copy of an imperial diploma of the emperor Louis II, dated 4 November 862. The document recorded the donation of the curtes of Guastalla and Luzzara to Louis’ wife, the empress Angilberga, who subsequently left the same lands to the monastery in her will. Abbot Gandolfo stated that the lost original of the imperial diploma had been furnished with a golden seal and three monks of S. Sisto testified on oath that they had read the document and seen and touched the seal. This event marked the beginning of a bitter dispute lasting three decades between the monastery of S. Sisto and the commune of Cremona over possession of Guastalla and Luzzara. Before it was finally resolved in 1227 it attracted the attention of three popes (Innocent III, Honorius III, and Gregory IX), two emperors (Otto IV and Frederick II), three papal legates (including Ugolino da Segni, the future Pope Gregory IX) as well as a large cast of Lombard bishops and abbots employed as papal judges-delegate. It arose principally as a result of Cremona’s attempt to gain control of an area on the south-eastern periphery of its territory or contado. This was not unusual in northern Italy in the twelfth and thirteenth centuries: powerful city communes were everywhere trying to push the boundaries of their political, fiscal, and judicial authority up to, and sometimes beyond, traditionally recognized limits. The Guastalla–Luzzara case is an extremely well-documented instance of this trend: 250 documents relating to it are transcribed together, more or less in sequence, in an early thirteenth-century register of the commune of Cremona known as Codice A. This documentary record reveals in detail the various strategies adopted by the commune of Cremona to achieve its goals and allows the historian to view the dispute against the complicated background of political alliances, power relationships, and war in the Po plain during this period. Moreover, such is the richness of documentation that the case also throws up numerous vivid details of human interest.

ObjectiveTo study longitudinal relationships between type 2 diabetes mellitus (T2DM), cortical thickness, and cognitive function in older people with normal cognition, mild cognitive impairment, and Alzheimer disease (AD).MethodsThe sample was derived from the Alzheimer's Disease Neuroimaging Initiative cohort who underwent brain MRI and cognitive tests annually for 5 years. Presence of T2DM was based on fasting blood glucose ≥7.0mml/L or the use of glucose-lowering agents. We used latent growth curve modeling to explore longitudinal relationships between T2DM, cortical thickness, and cognitive function, adjusting for relevant covariates and testing for interactions.ResultsThere were 124 people with T2DM (mean age 75.5 years, SD 6.2) and 693 without T2DM (mean age 75.1 years, SD 6.9) with at least 1 MRI available. AD and lower cortical thickness at study entry was associated with a lower chance of having a MRI available at each follow-up phase (all p < 0.001). T2DM was associated with lower baseline cortical thickness (p = 0.01). We found no direct effect of T2DM on decline in cortical thickness or cognitive function, but there was an indirect pathway linking T2DM and cognitive decline via baseline cortical thickness (β = −0.17, p = 0.022). There was an interaction between T2DM and education whereby the negative effect of T2DM on baseline cortical thickness was reduced in those with greater education (β = 0.34, p = 0.037). These associations changed minimally when adjusted for baseline cognitive diagnosis.ConclusionsIn an older cohort with low cerebrovascular disease burden, T2DM contributes to cognitive decline via neurodegeneration. Prior brain and cognitive reserve may protect against this effect.

Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer’s disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, ‘shape connections’ between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus.

Purpose To assess the efficacy of preoperative positron emission tomography (PET) to stage the ipsilateral hilum in resected non-small cell lung cancer (NSCLC). Methods and materials All patients who underwent surgery for NSCLC between 1995 and 2008 were evaluated. Patients who underwent preoperative PET imaging at our institution and had hilar nodal sampling were included. Those whose primary tumors extended to the hilum or who received preoperative chemotherapy or radiation therapy were excluded. All PET studies were interpreted by an attending nuclear medicine radiologist and were scored as positive or negative in the hilum or peribronchial area based on visual analysis alone. A 2-sided Fisher exact test compared patient subgroups. Results During the time interval, 1558 patients underwent surgery for NSCLC, of whom 484 were eligible for this analysis. The ipsilateral hilum was positive on preoperative PET in 107 patients. The median number of N1 lymph nodes sampled was 4 (range, 1-31). Positive ipsilateral N1 lymph nodes were identified pathologically in 91 patients (19%). Among the 91 patients with involved N1 lymph nodes, 40 were PET positive resulting in a sensitivity of 44%. Among 393 patients without pathologic involvement of hilar lymph nodes, 326 were PET negative resulting in a specificity of 83%. The positive predictive and negative predictive values were 37% and 86%, respectively. Conclusions Positron emission tomography appears to have limitations in staging the ipsilateral hilar lymph nodes. Invasive sampling is appropriate if treatment would differ based on the nodal status.

Brain imaging genetics intends to uncover associations between genetic markers and neuroimaging quantitative traits. Sparse canonical correlation analysis (SCCA) can discover bi-multivariate associations and select relevant features, and is becoming popular in imaging genetic studies. The L1-norm function is not only convex, but also singular at the origin, which is a necessary condition for sparsity. Thus most SCCA methods impose $${\ell }_{{\bf{1}}}$$ ℓ 1 -norm onto the individual feature or the structure level of features to pursuit corresponding sparsity. However, the $${\ell }_{{\bf{1}}}$$ ℓ 1 -norm penalty over-penalizes large coefficients and may incurs estimation bias. A number of non-convex penalties are proposed to reduce the estimation bias in regression tasks. But using them in SCCA remains largely unexplored. In this paper, we design a unified non-convex SCCA model, based on seven non-convex functions, for unbiased estimation and stable feature selection simultaneously. We also propose an efficient optimization algorithm. The proposed method obtains both higher correlation coefficients and better canonical loading patterns. Specifically, these SCCA methods with non-convex penalties discover a strong association between the APOE e4 rs429358 SNP and the hippocampus region of the brain. They both are Alzheimer’s disease related biomarkers, indicating the potential and power of the non-convex methods in brain imaging genetics.

Accurate prediction of Alzheimer’s disease (AD) is important for the early diagnosis and treatment of this condition. Mild cognitive impairment (MCI) is an early stage of AD. Therefore, patients with MCI who are at high risk of fully developing AD should be identified to accurately predict AD. However, the relationship between brain images and AD is difficult to construct because of the complex characteristics of neuroimaging data. To address this problem, we present a longitudinal measurement of MCI brain images and a hierarchical classification method for AD prediction. Longitudinal images obtained from individuals with MCI were investigated to acquire important information on the longitudinal changes, which can be used to classify MCI subjects as either MCI conversion (MCIc) or MCI non-conversion (MCInc) individuals. Moreover, a hierarchical framework was introduced to the classifier to manage high feature dimensionality issues and incorporate spatial information for improving the prediction accuracy. The proposed method was evaluated using 131 patients with MCI (70 MCIc and 61 MCInc) based on MRI scans taken at different time points. Results showed that the proposed method achieved 79.4% accuracy for the classification of MCIc versus MCInc, thereby demonstrating very promising performance for AD prediction.

This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ- subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs -0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ- subjects do.

Under Medicare’s Coverage with Evidence Development policy, PET using 18F-sodium fluoride (NaF PET) to identify osseous metastasis became a covered service if prospective registry data were collected. The National Oncologic PET Registry (NOPR) developed a NaF PET registry built on the foundation of its prior registry for PET with 18F-FDG. Men with prostate cancer represented 72% of the cases. Methods: Prospective data before and after NaF PET were collected from referring and interpreting physicians. The analysis set consisted of consenting men age 65 y or older with prostate cancer undergoing NaF PET for initial staging (IS, n = 1,024), suspected first osseous metastasis (FOM, n = 1,997), or suspected progression of osseous metastasis (POM, n = 510). Results: Referring physicians indicated that if NaF PET were not available, other advanced imaging (body CT, MR imaging, or 18F-FDG PET) would be their plan in about half of the cases. After NaF PET, the postimaging plan was revised to treatment in 77%, 52%, and 71% for IS, FOM, and POM, respectively. When intended management was classified as either treatment or nontreatment, the overall change in intended management ranged from 44% to 52% and from 12% to 16% if no effect was assumed for those cases with pre-PET plans for other imaging (imaging-adjusted impact). Interpreting physicians recorded definite findings of bone metastasis in 14%, 29%, and 76% for IS, FOM, and POM, respectively. The intended care patterns varied widely across indication and scan abnormality category combinations. Conclusion: NaF PET has high overall impact, principally related to its effect on replacing intended use of other advanced imaging. Its imaging-adjusted impact was similar to that observed with 18F-FDG PET for restaging or suspected recurrence in other cancer types.

Neuropathologic heterogeneity is often present among Alzheimer disease (AD) patients. We sought to determine whether amyloid imaging measures of AD are affected by concurrent pathologies. Thirty-eight clinically and pathologically defined AD and 17 nondemented patients with quantitative florbetapir F-18 (F-AV-45) positron emission tomography (PET) imaging during life and postmortem histological β-amyloid quantification and neuropathologic examination were assessed. AD patients were divided on the basis of concurrent pathologies, including those with Lewy bodies (LBs) (n = 21), white matter rarefaction (n = 27), severe cerebral amyloid angiopathy (n = 11), argyrophilic grains (n = 5), and TAR DNA binding protein-43 inclusions (n = 18). Many patients exhibited more than 1 type of concurrent pathology. The ratio of cortical to cerebellar amyloid imaging signal (SUVr) and immunohistochemical β-amyloid load were analyzed in 6 cortical regions of interest. All AD subgroups had strong and significant correlations between SUVr and histological β-amyloid measures (p μ 0.001). All AD subgroups had significantly greater amyloid measures versus nondemented patients, and mean amyloid measures did not significantly differ between AD subgroups. When comparing AD cases with and without each pathology, AD cases with LBs had significantly lower SUVr measures versus AD cases without LBs (p = 0.002); there were no other paired comparison differences. These findings indicate that florbetapir-PET imaging is not confounded by neuropathological heterogeneity within AD.

Objective Many patients with non–small cell lung cancer have positive mediastinal lymph nodes on preoperative positron emission tomography (PET) but do not have mediastinal involvement after surgery. The prognostic significance of this discordance was assessed. Methods This Institutional Review Board–approved study evaluated patients treated with upfront surgery at Duke Cancer Institute (Durham, NC) for non–small cell lung cancer from 1995 to 2008. Those staged with PET with pN0-1 disease after negative invasive mediastinal assessment were included. Mediastinal lymph nodes were scored as positive or negative based on visual analysis of the preoperative PET. Clinical outcomes of the PET-positive and PET-negative cohorts were estimated using the Kaplan-Meier method and compared using a log-rank test. Prognostic factors were assessed using a multivariate analysis. Results A total of 547 patients were assessed, of whom 105 (19%) were PET positive in the mediastinum. The median number of mediastinal lymph node stations sampled was 4 (range, 1-9). The 5-year risk of local recurrence was 26% in PET-positive versus 21% in PET-negative patients ( P = .50). Patterns of local failure were similar between the 2 groups. Distant recurrence (35% vs 29%; P = .63) and overall survival (44% vs 54%; P = .52) were comparable for PET-positive and PET-negative patients. On multivariate analysis, a positive PET was not significant for local recurrence (hazard ratio [HR], 1; P = 1), distant recurrence (HR, 0.82; P = .42), or overall survival (HR, 1.08; P = .62). Conclusions Patients with positive mediastinal lymph nodes on preoperative PET, but negative on histologic analysis, are not at increased risk of disease recurrence. Pathologic staging remains the standard.

The purpose of this study was to determine whether certain factors in the preparation and use of 99mTc-sulfur colloid affected the number of sentinel lymph nodes (SLNs) detected during SLN mapping and during intraoperative SLN identification. The factors that were investigated included the use of a dry heat block versus a hot water bath to heat the 99mTc-sulfur colloid bulk vial, amount of 99m TcOH4 2 added to form the sulfur colloid particles, time between the unit dose calibration and the injection of the dose, and breast quadrant in which the injection occurred. Methods: Data were collected retrospectively and quantitatively analyzed from images and reports of 488 patients with breast cancer who had undergone SLN mapping and intraoperative SLN identification from January 1, 2008, to June 30, 2011, inclusive. The dependent variables assessed were the number of SLNs visualized during lymphoscintigraphy, number of radioactive SLNs removed during surgery, and total number of lymph nodes removed intraoperatively. Results: There was no significant difference in outcomes when comparing the amount of 99m TcOH4 2 added during the preparation process to form the sulfur colloid particles, time between the unit dose calibration time and the time that the unit doses were injected, or location in the breast tissue in which the unit dose was administered. Initially, there were observed significant differences in outcomes when the heating methods used to prepare the 99m Tc-sulfur colloid were compared. When the increased number of patients who were administered a calibrated unit dose activity of 74 MBq in the group using a dry heat block preparation method was taken into account, however, the findings were not significant. Conclusion: The use of a dry heat block versus a hot water bath to heat the 99mTc-sulfur colloid bulk vial, amount of 99m TcOH4 2 added to form sulfur colloid particles, time between the unit dose calibration and the injection of the dose, and breast quadrant in which the injection occurred do not affect the number of SLNs detected during SLN mapping and during intraoperative SLN identification.

Purpose While consolidation radiation therapy (i.e., RT administered after chemotherapy) is routine treatment for patients with early-stage diffuse large B-cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is controversial. Methods and Materials Cases of patients with stage III-IV DLBCL treated from 1991 to 2009 at Duke University, who achieved a complete response to chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. Results Seventy-nine patients were identified. Chemotherapy (median, 6 cycles) consisted of anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or other (13%). Post-chemotherapy imaging consisted of positron emission tomography (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%). Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38 (48%) patients. Receipt of consolidation RT was associated with improved in-field control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs. 65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%, respectively, p = 0.15) when compared to patients who did not receive consolidation RT. On multivariate analysis, no RT was predictive of increased risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event-free survival (HR, 4.3, p = 0.014). Conclusions Patients with stage III-IV DLBCL who achieve negative post-chemotherapy imaging have improved in-field control and event-free survival with low-dose consolidation RT.

Summary Background Results of previous studies have shown associations between PET imaging of amyloid plaques and amyloid-β pathology measured at autopsy. However, these studies were small and not designed to prospectively measure sensitivity or specificity of amyloid PET imaging against a reference standard. We therefore prospectively compared the sensitivity and specificity of amyloid PET imaging with neuropathology at autopsy. Methods This study was an extension of our previous imaging-to-autopsy study of participants recruited at 22 centres in the USA who had a life expectancy of less than 6 months at enrolment. Participants had autopsy within 2 years of PET imaging with florbetapir ( 18 F). For one of the primary analyses, the interpretation of the florbetapir scans (majority interpretation of five nuclear medicine physicians, who classified each scan as amyloid positive or amyloid negative) was compared with amyloid pathology (assessed according to the Consortium to Establish a Registry for Alzheimer's Disease standards, and classed as amyloid positive for moderate or frequent plaques or amyloid negative for no or sparse plaques); correlation of the image analysis results with amyloid burden was tested as a coprimary endpoint. Correlation, sensitivity, and specificity analyses were also done in the subset of participants who had autopsy within 1 year of imaging as secondary endpoints. The study is registered with ClinicalTrials.gov, number NCT 01447719 (original study NCT 00857415). Findings We included 59 participants (aged 47–103 years; cognitive status ranging from normal to advanced dementia). The sensitivity and specificity of florbetapir PET imaging for detection of moderate to frequent plaques were 92% (36 of 39; 95% CI 78–98) and 100% (20 of 20; 80–100%), respectively, in people who had autopsy within 2 years of PET imaging, and 96% (27 of 28; 80–100%) and 100% (18 of 18; 78–100%), respectively, for those who had autopsy within 1 year. Amyloid assessed semiquantitatively with florbetapir PET was correlated with the post-mortem amyloid burden in the participants who had an autopsy within 2 years (Spearman ρ=0·76; p Interpretation The results of this study validate the binary visual reading method approved in the USA for clinical use with florbetapir and suggest that florbetapir could be used to distinguish individuals with no or sparse amyloid plaques from those with moderate to frequent plaques. Additional research is needed to understand the prognostic implications of moderate to frequent plaque density. Funding Avid Radiopharmaceuticals.

Florbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in subjects at risk for progressive cognitive decline.A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aβ+) or negative (Aβ-) for pathologic levels of β-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.In both MCI and CN, baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog (p0.01) and Clinical Dementia Rating-sum of boxes (CDR-SB) (p0.02). In MCI Aβ+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p0.01), CDR-SB (p0.03), a memory measure, DSS, and MMSE (p0.05). Aβ+ MCI tended to convert to AD dementia at a higher rate than Aβ- subjects (p0.10).Florbetapir PET may help identify individuals at increased risk for progressive cognitive decline.

OBJECTIVES Positron emission tomography protocols conventionally use a constant scan time per bed position (BP). It may be optimal to spend more time scanning some body sections, particularly the more attenuating sections. The relatively consistent tapering of legs may allow a single, variable-time protocol that could reduce or redistribute time and equalize image quality throughout the leg. Reducing the total scan time will limit the opportunity for motion, which can reduce imaging artefacts and improves image fusion, will improve a patient's experience, and will yield the biggest gains in time for the tallest patients. METHODS Leg dimensions were studied in 55 adult positron emission tomography/computed tomography scans. Image quality versus size was parameterized using bottle phantoms (diameters, 4.5-19.7 cm) filled with identical 18F-fluorodeoxyglucose concentrations, positioned as legs and imaged. An exponential relationship of diameter to noise was fit to the data, which defined the noise-equalizing, variable-time protocol. RESULTS Of 55 patient leg studies, 94.5% (52/55) had leg diameters that were less than ± 7.5% of the mean leg diameter for other patients of similar height. To equalize noise throughout the leg, relative scan times from superior to inferior as a function of BP are (1, 0.65, 0.45, 0.36, 0.30, and 0.25). CONCLUSION Variable time compared with a constant-time protocol can require 75% less time for some BPs and half the total acquisition time. A variable-time protocol to reduce time has been implemented.

Uric acid (UA) is known to activate the NLRP3 (Nacht, leucine-rich repeat and pyrin domain containing protein 3) inflammasome. When activated, the NLRP3 (also known as NALP3) inflammasome leads to the production of IL-18 and IL-1β. In this cohort of subjects with knee osteoarthritis (OA), synovial fluid uric acid was strongly correlated with synovial fluid IL-18 and IL-1β. Synovial fluid uric acid and IL-18 were strongly and positively associated with OA severity as measured by both radiograph and bone scintigraphy, and synovial fluid IL-1β was associated with OA severity but only by radiograph. Furthermore, synovial fluid IL-18 was associated with a 3-y change in OA severity, on the basis of the radiograph. We conclude that synovial fluid uric acid is a marker of knee OA severity. The correlation of synovial fluid uric acid with the two cytokines (IL-18 and IL-1β) known to be produced by uric acid-activated inflammasomes and the association of synovial fluid IL-18 with OA progression, lend strong support to the potential involvement of the innate immune system in OA pathology and OA progression.

This study seeks to assess the impact of dedicated brain positron emission tomography (PET) with 2-deoxy-2-[(18)F]fluoro-D-glucose on intended management of patients with primary and metastatic brain tumors.We analyzed demographic characteristics and evaluated change in intended management after PET, using previously described metrics, for patients in the National Oncologic PET Registry (NOPR) undergoing dedicated brain PET. For cases of primary brain tumors, comparisons to the overall NOPR cohort were made. PATIENT PROFILE: Between December 2006 and April 2009, 509 dedicated brain PET scans were done on 479 patients--367 (72.1%) for suspected or proven primary brain tumors and 142 (27.9%) for brain metastases. Compared with the overall NOPR cohort, subjects in the dedicated brain cohort were younger (41.3% less than 65 years vs. 10.5% overall, p0.0001) and more frequently had functional limitations from their cancers (78.6% vs. 62.3% overall; odds ratio (OR) 2.2, 95% CI 1.8-2.8).The pre-PET patient management plans in the primary brain tumor and metastasis subgroups were similar. A pre-PET plan of tissue biopsy was slightly more frequent than one of the treatments (31.3% vs. 28.6%) in the primary brain tumor subgroup and was more common than in the overall NOPR cohort (14.2%; OR 2.8, 95% CI 2.2-3.5). Changes from treatment to non-treatment also were more frequent than in the overall NOPR cohort (13.4% vs. 7.7%; OR 1.9, 95% CI 1.3-2.5).Among NOPR patients, dedicated brain PET was associated with similar net changes in intended management as in the overall NOPR cohort. However, brain PET patients were younger, more likely to be symptomatic, and less likely to have a change in management from non-treatment to treatment as a post-PET plan.

The objective of this study, which is related to human brain SPECT, was to increase the sensitivity of a triple-camera SPECT system and reduce statistical noise in reconstructed images using a combination of converging collimators. The reason for combining collimators is to ensure both high sensitivity and sufficient sampling without trading off spatial resolution. Methods: A high-sensitivity half-cone-beam (HCB) collimator, designed specifically for brain imaging, was combined with other collimators and compared with conventional parallel-beam and fanbeam circular orbit acquisitions. For comparison, previously studied HCB collimation with a circle-and-helix data acquisition trajectory was also included in this study. Simulations of the Hoffman 3-dimensional brain phantom were performed to calculate the efficiencies of collimators and their combinations and to quantitatively evaluate reconstruction bias, statistical noise, and signal-to-noise ratios in the reconstructed images. Experimental brain phantom data were also acquired and compared for different acquisition types. Finally, a patient brain scan was obtained with a combination of HCB and fanbeam collimators and compared with a triple-fanbeam circular orbit acquisition. Results: A combination of 2 HCB collimators and 1 fanbeam collimator, compared with a triple-fanbeam collimator, can increase the photon detection efficiency by 27% and by more than a factor of 2, compared with triple-parallel-hole collimation, with equal spatial resolution measured on the axis of rotation. Quantitative analysis of reconstruction bias and visual analysis of the images showed no signs of sampling artifacts. Reconstructed images in the simulations, experimental brain phantom, and patient brain scans showed improved quality with this collimator combination due to increased sensitivity and reduced noise. Lesion visibility was also improved, as confirmed by signal-to-noise ratios. Alternatively, triple-HCB circle-and-helix acquisition has also shown competitive results, with a slight disadvantage in axial sampling and implementation procedure. Conclusion: Combined HCB and fanbeam collimation is a promising approach for high-sensitivity brain SPECT.

Background CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT ( r = −0.28, p = 0.0001) and SRWA ( r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

This is a first of many phase 1 study of Ultratrace Iobenguane I-131 (Ultratrace 131I-MIBG; Molecular Insight Pharmaceuticals, Inc., Cambridge, MA). High-specific-activity Ultratrace 131I-MIBG may provide improved efficacy and tolerability over carrier-added 131I-MIBG. We investigated the pharmacokinetics (PK), radiation dosimetry, and clinical safety in 11 patients with confirmed pheochromocytoma/paraganglioma (Pheo) or carcinoid tumors. A single 5.0-mCi (185 MBq) injection of Ultratrace 131I-MIBG, supplemented with 185 microg of unlabeled MIBG to simulate the amount of MIBG anticipated in a therapeutic dose, was administered. Over 120 hours postdose, blood and urine were collected for PK, and sequential whole-body planar imaging was performed. Patients were followed for adverse events for 2 weeks. Ultratrace 131I-MIBG is rapidly cleared from the blood and excreted in urine (80.3% +/- 2.8% of dose at 120 hours). For a therapeutic administration of 500 mCi (18.5 GBq), our estimate of the projected dose is 1.4 Gy for marrow and 10.4 Gy for kidneys. Safety results showed 12 mild adverse events, all considered unrelated to study drug, in 8 of 11 patients. These findings support the further development of Ultratrace 131I-MIBG for the treatment of neuroendocrine tumors, such as metastatic Pheo and carcinoid.

Positron emission tomography (PET) imaging at more than 1 h after 2-deoxy-2-[18F]fluoro-d-glucose (FDG) administration may result in less blood pool activity and possibly decreased normal FDG uptake in tissues such as liver. Lower normal background activity could be an important component of improved image contrast on delayed imaging. Increasing FDG uptake in normal organs, however, may mitigate the beneficial effects of blood pool clearance. The purpose of this study is to determine the normal tissue and blood pool FDG uptake at 1 and 3 h after injection. Ninety-nine patients with known or suspected malignancy referred for FDG-PET–computed tomography (CT) were retrospectively evaluated. PET imaging was performed at either 1 h (60 ± 15 min; n = 50) or at 3 h (180 ± 15 min; n = 49) after FDG administration. Normal tissue FDG uptake without involvement by malignancy or influenced by artifact (misregistration, “brown fat,” focal muscle uptake, focal atherosclerotic disease) was confirmed by inspection of both the PET and CT scans. Aortic blood pool, adipose tissue, bone marrow, cerebellum, liver, lungs, muscle, and spleen were quantitatively evaluated by CT-guided region of interest analysis in three contiguous slices. Mean standardized uptake values (SUVs) were analyzed using one-way analysis of variance. Mean SUVs on the 3- versus 1-h images were significantly lower for aortic blood pool 13% (p

SUMMARY Twenty-two previously normal children and adolescents who suffered a severe, non-penetrating traumatic brain injury had PET during rehabilitation at a median of 1–5 months after the injury. Outcome was assessed at a median of 25 months after brain injury. 16 subjects had CT or MRI within 24 days of PET and 11 subjects had a second PET at the point of outcome (median 28 months after first PET). The PET score (obtained by adding the score of 15 brain regions: normal metabolism = 1; reduced = 0) was significantly associated with the clinical outcome measure. PET earlier than 12 weeks after head trauma correlated with outcome, but later PET did not. PET scores improved significantly between rehabilitation and outcome for the 11 subjects who had two PETs, but improvement was not associated with improvement in clinical condition. PET score did not add to the amount of variance explained in the last regression model for prediction of outcome when the results of contemporaneous CT/MRI and clinical condition were taken into account. The data suggest that routine PET during rehabilitation is no more useful than contemporaneous CT or MRI for prediction of outcome. RESUME Tomographies aemission de positrons 18-fiuoroglucose (PET) chez des enfants et adolescents, apres un traumatisme cerebral Des PET ont ete pratiques durant la reeducation, en moyenne 1–5 mois apres l'accident, chez 22 enfants et adolescents normaux avant l'accident, ayant subi un traumatisme cerebral grave sans penetration. Le devenir fut evaluea une moyenne de 25 mois apres la lesion cerebrale. Un scanner ou une LR.M. furent pratiques dans les 24 jours du PET chez 16 sujets, et 11 sujets beneficierent d'un second PET lors de l'evaluation du denenir (en moyenne 28 mois apres le premier PET). Le score PET (obtenu en additionnant les scores de 15 regions cerebrales: metabolisme normal = 1, metabolisme reduit = 0) etait significativement correle avec l'evaluation clinique du devenir. Les PET de moins de 12 semaines apres le truamatisme crânien etaient correles avec le devenir, mais non les PET plus tardifs. Les scores PET s'amelioraient significativement entre la reeducation et l'evaluation du devenir pour les 11 sujets ayant eu deux PET, mais l'amelioration n'etait pas associee a une amelioration de l'etait clinique. Ces donnees suggerent que le PET durant la reeducation n'est pas plus utile que des scanners ou IRM aux memes dates, dans la prediction du devenir. ZUSAMMENFASSUNG 18 Fluoro-D-Glukose Positronen-Emissionstomographie bet Kindern und Jugendlichen mil Hirntraumen 22 zuvor gesunde Kinder und Jugendliche, die ein schweres nicht penetrierendes Hirntrauma hatten, wurden wahrend der Rehabilitation etwa 1–5 Monate nach der Verletzung durch ein PET untersucht. Durchschnittlich 25 Monate nach dem Hirntrauma wurde der Outcome beurteilt. 16 Patienten hatten innerhalb von 24 Tagen nach dem PET ein CT oder MRI und 11 hatten ein zweites PET bei der Abschlusuntersuchung (im Mittel 28 Monate nach dem ersten PET). Der PET Score (errechnet durch Addition der Scores von 15 Hirnregionen: normaler Stoffwechsel = 1; verminderter = 0) hatte eine signifikante Relation zum klinischen Abschlusbefund. PET bis zu 12 Wochen nach dem Schadeltrauma korrelierte mit dem Outcome, spatere PETs jedoch nicht. Bei den 11 Patienten, die zwei PETs hatten, besserten sich die PET Scores signifikant in dem Zeitraum von der Rehabilitation bis zur Abschlusuntersuchung, aber dies war nicht gleichbedeutend mit eincr Besserung des klinischen Befundes. Die Daten zeigen, das das Routine-PET wahrend der Rehabilitation fur die Prognose des Outcomes keine weitere Aussagekraft hat als ein zur gleichen Zeit angefertigtes CT oder MRL RESUMEN Tomografia por emision de positrons con 18-fluorodesoxiglucosa en ninos y adolescentes con lesion traumatica cerebral Veintidos ninos y adolescentes previamente normales, que sufrieron un trauma cerebral no penetrante, fueron examinados con PET durante la rehabilitacion, un promedio de 1,5 meses despues de la lesion. El curso fue evaluado un promedio de 25 meses despues de la lesion. 16 individuos fueron examinados con TAC o con IRM a los 25 meses de la PET y a 11 se les aplico de nuevo la PET a los 28 meses de promedio despues de la primera PET. El puntaje de la PET (obtenida sumando los puntajes de 15 regiones cerebrales. metabolismo normal = 1; reduciodo = 0) estaba significativamente asociado a la medicion clinica de la recuperacion. Una PET realizada antes de las 12 semanas despues del trauma cerebral, se relacionaba con el curso, pero hecha mas tarde y no. Los puntajes de la PET mejoraban significativamente entre la rehabilitation y la recuperacion en los 11 casos con dos PET, pero la mejoria no se acompanaba de una mejoria clinica. Los datos sugieren que la exploracion rutinario con PET no es mas util que la TAC o la IRM, realizados contemporaneamente, con respecto a la prediction del curso posterior.

Carcinoid tumors account for less than 1% of all malignancies and the majority arise in the gastrointestinal system. These tumors are slow growing compared with adenocarcinomas and they differ from the other neuroendocrine malignancies by their protean clinical presentation. Carcinoid tumors were previously considered indolent, but they can manifest malignant characteristics with metastatic spread which often results in a poor prognosis. Although there have been advances in diagnostic and treatment modalities, carcinoid tumors are still often diagnosed late, often when the tumor has metastasized and patients develop carcinoid syndrome. Diagnosis, prognosis and treatment options are based on biochemical markers and imaging investigations. High concentration of urinary 5-HIAA, elevated plasma serotonin and chromogranin A levels help to establish the initial diagnosis of carcinoid tumors. In addition to the CT and MRI, molecular imaging modalities such as OctreoScan, MIBG imaging and more recently PET imaging are vital in detection of primary malignancy and metastatic involvement. Surgery is the mainstay of treatment of nonmetastatic carcinoid tumors. Cytotoxic chemotherapy is not beneficial due to the chemoresistant nature of these tumors. Because carcinoid tumors express somatostatin receptors, somatostatin analogues, which inhibit the release of serotonin and other neuroendocrine peptides, are often used, but their use is limited to symptom control. Treatment using high doses of radionuclides such as radiolabeled somatostatin analogues and MIBG is a more recent option which offers a definite advantage in management. In this article, we review typical features of the carcinoid tumors, examine contemporary methods of detecting and assessing carcinoid tumors and discuss the role of various diagnostic and therapeutic options.

The majority of pheochromocytomas and paragangliomas are benign, with malignancy occurring in approximately 10% of pheochromocytoma patients. The malignancy rate among paragangliomas is 15–35% or higher if associated with succinate dehydrogenase B gene mutations. The 5-year mortality rate in malignant pheochromocytoma and paraganglioma is nearly 50%. Malignancy of both pheochromocytoma and paraganglioma is determined by the existence of metastasis or local invasion and not by the cellular characteristics. There are no known clinical, biochemical or histopathological differences between pheochromocytoma and paraganglioma. Metaiodobenzylguanidine (MIBG) radiolabeled with either 123 I or 131 I has been used to diagnose neuroendocrine tumors such as paraganglioma and pheochromocytoma, and 131 I-MIBG has been used to treat these tumors. The role of radioiodinated MIBG in treating neuroendocrine tumors is still being evaluated. More recently, no-carrier-added (nca) MIBG has become available, and the advantages of nca MIBG over ca MIBG are being demonstrated. This article reviews the biology of paragangliomas and pheochromocytomas, the role of MIBG imaging in the diagnosis of these tumors and the role of both ca and nca 131 I-MIBG in the treatment of these tumors. New data on nca 131 I-MIBG in the therapy of these tumors are included.

Adults with primary malignant glioma have an unacceptably poor outcome. Although temozolomide plus radiotherapy improves survival of newly diagnosed glioblastoma multiforme (GBM) patients,1 most patients develop tumor progression within 1 – 2 years. Outcome following recurrence is poor.2 Most tumors recur at or adjacent to the site of origin, indicating that failure to eradicate local tumor growth is a major factor contributing to poor outcome.3 For this reason, we have focused on augmenting local control to improve overall outcome by administering tumor-associated radiolabeled monoclonal antibodies (mAbs) directly into spontaneous tumor cysts, surgically created resection cavities (SCRCs), the intrathecal space, and solid tumors.4–8 Tenascin, an extracellular matrix hexabrachion glycoprotein, is expressed ubiquitously in several cancers, including high-grade gliomas, but not in normal brain.9,10 mAb 81C6, a murine isotype 2b immunoglobulin G (IgG2b) that binds to an alternatively spliced region of tenascin,9–12 reacts specifically with tenascin-expressing tumors.13 When labeled with 131I, 81C6 delays tumor growth and prolongs survival in flank and intracranial human xenograft models.14,15 An initial human experience demonstrated the specificity of 131I-labeled murine 81C6 (131I-81C6) mAb compared to 125I-labeled nonspecific IgG2b mAb but also revealed limited intratumor penetration following intravenous or intraarterial administration.16 Hence, subsequent studies incorporated administration into an SCRC, tumor cyst, or intrathecal space. Prior phase I studies established the maximum tolerated dose (MTD) of 131I-81C6 injected into the SCRC of patients with newly diagnosed and recurrent malignant brain tumors to be 120 mCi and 100 mCi, respectively.7,8 Phase II studies demonstrated that patients treated with 131I-81C6 had favorable overall survival compared to established historical controls.4,5 Based on constraints of our U.S. Food and Drug Administration (FDA)-approved phase I and II studies, patients received a “fixed” dose of 131I-81C6 in which the administered level of radioactivity was the same among groups of patients. As a result of this design, 131I dosages were not adjusted to compensate for patient-specific variables such as SCRC volume and SCRC residence time. Dosimetry of patients treated on these studies revealed a wide range of radiation absorbed doses at the SCRC margin. Moreover, outcome correlated with delivered radiation dose to the SCRC. Specifically, patients who received less than 44 Gy were more likely to develop recurrent tumor, whereas those who received significantly more than 44 Gy were more likely to develop radionecrosis. Therefore, a 44-Gy boost to the SCRC margin was considered optimal.17 We now report a pilot study using a novel, patient-specific dosing strategy of 131I-81C6 designed to achieve a 44-Gy boost to the 2-cm SCRC margin in adults with newly diagnosed malignant gliomas.

The presence of contrast materials on computed tomography (CT) images can cause problems in the attenuation correction of positron emission tomography (PET) images. These are because of errors converting the CT attenuation of contrast to 511-keV attenuation and by the change in tissue enhancement over the duration of the PET emission scan. Newer CT-based attenuation correction (CTAC) algorithms have been developed to reduce these errors. To evaluate the effectiveness of the modified CTAC technique, we performed a retrospective analysis on 20 patients, comparing PET images using unenhanced and contrast-enhanced CT scans for attenuation correction. A phantom study was performed to simulate the effects of contrast on radiotracer concentration measurements. There was a maximum difference in calculated radiotracer concentrations of 5.9% within the retrospective data and 7% within the phantom data. Using a CTAC algorithm that de-emphasizes high-density areas, contrast-enhanced CT can be used for attenuation mapping without significant errors in quantitation.

alpha-Particle-emitting radionuclides, such as (211)At, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of the much shorter range and more potent cytotoxicity of alpha-particles than of beta-particles, (211)At-labeled agents may be ideal for the eradication of tumor cells remaining after surgical debulking of malignant brain tumors. The main goal of this study was to investigate the feasibility and safety of this approach in patients with recurrent malignant brain tumors.Chimeric antitenascin monoclonal antibody 81C6 (ch81C6) (10 mg) was labeled with 71-347 MBq of (211)At by use of N-succinimidyl 3-[(211)At]astatobenzoate. Eighteen patients were treated with (211)At-labeled ch81C6 ((211)At-ch81C6) administered into a surgically created resection cavity (SCRC) and then with salvage chemotherapy. Serial gamma-camera imaging and blood sampling over 24 h were performed.A total of 96.7% +/- 3.6% (mean +/- SD) of (211)At decays occurred in the SCRC, and the mean blood-pool percentage injected dose wasor = 0.3. No patient experienced dose-limiting toxicity, and the maximum tolerated dose was not identified. Six patients experienced grade 2 neurotoxicity within 6 wk of (211)At-ch81C6 administration; this neurotoxicity resolved fully in all but 1 patient. No toxicities of grade 3 or higher were attributable to the treatment. No patient required repeat surgery for radionecrosis. The median survival times for all patients, those with glioblastoma multiforme, and those with anaplastic astrocytoma or oligodendroglioma were 54, 52, and 116 wk, respectively.This study provides proof of concept for regional targeted radiotherapy with (211)At-labeled molecules in oncology. Specifically, the regional administration of (211)At-ch81C6 is feasible, safe, and associated with a promising antitumor benefit in patients with malignant central nervous system tumors.

To prospectively determine feasibility of evaluating murine left ventricular (LV) function with electrocardiographically (ECG)-gated blood pool single photon emission computed tomography (SPECT).All animal studies had institutional animal care and use committee approval. SPECT was performed with conventional time-binned acquisition (eight frames per ECG cycle) in normal mice (normal group A, n = 6) and mice with myocardial infarction (MI) (n = 8). To determine feasibility of high temporal resolution and rapid data acquisition, another group of normal mice (normal group B, n = 4) underwent imaging with conventional (eight-frame) time-binned and list-mode (LM) acquisitions. LM acquisitions were reconstructed with eight and 16 frames per ECG cycle and 10 minutes of data (short LM). SPECT images were assessed visually, and LV-to-lung background activity ratios were calculated. LV end-systolic and end-diastolic volumes were defined with a phase analysis and threshold method. LV ejection fraction (LVEF) was calculated from LV volumes and count-based methods (n = 18 mice). Fractional shortening (FS) at echocardiography defined MI dysfunction (mild MI: FSor = 50%; severe MI: FS50%). Group means were compared for significant differences with analysis of variance.ECG-gated blood pool SPECT demonstrated normal, concentric LV contraction in all normal mice (n = 10). LV-to-lung background ratio was more than 10:1 (range, 10.3-29.4; n = 18). Focal wall motion abnormalities were detected at SPECT both visually and with phase analysis in all mice with severe MI (n = 5). Mice with severe MI had significantly lower LVEF than normal group A mice (32% +/- 14 [standard deviation] vs 64% +/- 8%; P.001). All mice with mild MI (n = 3) had normal contraction and LVEF. In paired acquisitions in normal group B mice, all reconstructions (n = 16) showed normal LV contraction. LVEF was not significantly different (P = .88) between time-binned (71% +/- 12), eight-frame LM (71% +/- 12), 16-frame LM (77% +/- 10), and short LM (73% +/- 14) reconstructions.Murine LV functional assessment is feasible with high spatial and temporal resolution ECG-gated blood pool SPECT. LV dysfunction can be quantified and focal wall motion abnormalities detected in the MI model of heart failure.

Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that target-tissue anatomy and patient-specific physiology play a major role in drug distribution using this technique. In this study, we retrospectively tested the ability of a software algorithm using MR diffusion tensor imaging to predict patient-specific drug distributions by CED. A tumor-targeted cytotoxin, cintredekin besudotox (interleukin 13–PE38QQR), was coinfused with iodine 123–labeled human serum albumin (123I-HSA), in patients with recurrent malignant gliomas. The spatial distribution of 123I-HSA was then compared to a drug distribution simulation provided by the software algorithm. The algorithm had a high sensitivity (71.4%) and specificity (100%) for identifying the high proportion (7 of 14) of catheter trajectories that failed to deliver drug into the desired anatomical region ( p = 0.021). This usually occurred when catheter trajectories crossed deep sulci, resulting in leak of the infusate into the subarachnoid cerebrospinal fluid space. The mean concordance of the volume of distribution at the 50% isodose level between the actual 123I-HSA distribution and simulation was 65.75% (95% confidence interval [CI], 52.0%–79.5%), and the mean maximal in-plane deviation was less than 8.5 mm (95% CI, 4.0–13.0 mm). The use of this simulation algorithm was considered clinically useful in 84.6% of catheters. Routine use of this algorithm, and its further developments, should improve prospective selection of catheter trajectories, and thereby improve the efficacy of drugs delivered by this promising technique.

To retrospectively compare the sensitivity of a dedicated fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) protocol versus a standard whole-body PET/CT protocol for detection of head and neck cancer, with biopsy and follow-up as reference standards.Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. Dedicated and standard PET/CT protocols were performed in a phantom and in 55 patients suspected of having head and neck cancer (28 men, 27 women; age range, 21-79 years). The neck phantom contained four 4.4-9.8-mm-diameter spheres. Standard protocol consisted of a midcranium to proximal thigh emission scan of 2-4 minutes per bed position. Dedicated protocol was an 8-minute head and neck scan. Reconstructed field of view and pixel size, respectively, were 30 cm and 2.34 mm for the dedicated and 50 cm and 3.91 mm for the standard protocol. FDG uptake was evaluated visually and semiquantitatively by using standardized uptake values (SUVs). Mean SUV was compared between dedicated and standard protocols with a t test modified for clustered sampling. Receiver operating characteristic (ROC) curves were calculated. A two-tailed P value was used.In the phantom study, a larger percentage difference (20%-27%) in sphere-to-background ratios with the dedicated than with the standard protocol was observed for 6.0-9.8-mm spheres. In the clinical study, a total of 149 lymph nodes were identified. Five malignant and six benign lymph nodes (mean diameter, 7.1 mm) were visually identified with the dedicated protocol only. SUVs with the dedicated protocol were significantly higher than those with the standard protocol (P.001). Area under the ROC curve was 0.94 for the dedicated and 0.92 for the standard protocol (P=.56).FDG PET with either the standard or dedicated protocol was more sensitive than CT for evaluating head and neck lymph nodes. The dedicated protocol improved the detectability of smaller nodes.