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BACKGROUND. Imaging biomarkers of response to neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDA) are needed to optimize treatment decisions and long-term outcomes. OBJECTIVE. The purpose of this study was to investigate metrics from PET/MRI and CT to assess pathologic response of PDA to NAT and to predict overall survival (OS). METHODS. This retrospective study included 44 patients with 18F-FDG-avid borderline resectable or locally advanced PDA on pretreatment PET/MRI who also underwent post-NAT PET/MRI before surgery between August 2016 and February 2019. Carbohydrate antigen 19-9 (CA 19-9) level, metabolic metrics from PET/MRI, and morphologic metrics from CT (n = 34) were compared between pathologic responders (College of American Pathologists scores 0 and 1) and nonresponders (scores 2 and 3). AUCs were measured for metrics significantly associated with pathologic response. Relation to OS was evaluated with Cox proportional hazards models. RESULTS. Among 44 patients (22 men, 22 women; mean age, 62 ± 11.6 years), 19 (43%) were responders, and 25 (57%) were nonresponders. Median OS was 24 months (range, 6-42 months). Before treatment, responders and nonresponders did not differ in CA 19-9 level, metabolic metrics, or CT metrics (p > .05). After treatment, responders and nonresponders differed in complete metabolic response (CMR) (responders, 89% [17/19]; nonresponders, 40% [10/25]; p = .04], mean change in SUVmax (ΔSUVmax; responders, -70% ± 13%; nonresponders, -37% ± 42%; p < .001), mean change in SUVmax corrected to serum glucose level (ΔSUVgluc) (responders, -74% ± 12%; nonresponders, -30% ± 58%; p < .001), RECIST response on CT (responders, 93% [13/14]; nonresponders, 50% [10/20]; p = .02)], and mean change in tumor volume on CT (ΔTvol) (responders, -85% ± 21%; nonresponders, 57% ± 400%; p < .001). The AUC of CMR for pathologic response was 0.75; ΔSUVmax, 0.83; ΔSUVgluc, 0.87; RECIST, 0.71; and ΔTvol 0.86. The AUCs of bivariable PET/MRI and CT models were 0.83 (CMR and ΔSUVmax), 0.87 (CMR and ΔSUVgluc), and 0.87 (RECIST and ΔTvol). OS was associated with CMR (p = .03), ΔSUVmax (p = .003), ΔSUVgluc (p = .003), and RECIST (p = .046). CONCLUSION. Unlike CA 19-9 level, changes in metabolic metrics from PET/MRI and morphologic metrics from CT after NAT were associated with pathologic response and OS in patients with PDA, warranting prospective validation. CLINICAL IMPACT. Imaging metrics associated with pathologic response and OS in PDA could help guide clinical management and outcomes for patients with PDA who undergo emergency therapeutic interventions.

Purpose Our previous work demonstrated that 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) positron emission tomography (PET) is sensitive and specific for identifying regions of high density and biologically aggressive glioblastoma. The purpose of this prospective phase 2 study was to determine the safety and efficacy of biologic-guided, dose-escalated radiation therapy (DERT) using 18F-DOPA PET in patients with glioblastoma. Methods and Materials Patients with newly diagnosed, histologically confirmed glioblastoma aged ≥18 years without contraindications to 18F-DOPA were eligible. Target volumes included 51, 60, and 76 Gy in 30 fractions with a simultaneous integrated boost, and concurrent and adjuvant temozolomide for 6 months. 18F-DOPA PET imaging was used to guide DERT. The study was designed to detect a true progression-free survival (PFS) at 6 months (PFS6) rate ≥72.5% in O6‐methylguanine methyltransferase (MGMT) unmethylated patients (DE-Un), with an overall significance level (alpha) of 0.20 and a power of 80%. Kaplan-Meier analysis was performed for PFS and overall survival (OS). Historical controls (HCs) included 139 patients (82 unmethylated) treated on prospective clinical trials or with standard RT at our institution. Toxicities were evaluated with Common Terminology Criteria for Adverse Events v4.0. Results Between January 2014 and December 2018, 75 evaluable patients were enrolled (39 DE-Un, 24 methylated [DE-Mth], and 12 indeterminate). PFS6 for DE-Un was 79.5% (95% confidence interval, 63.1%-90.1%). Median PFS was longer for DE-Un patients compared with historical controls (8.7 months vs 6.6 months; P = .017). OS was similarly longer, but the difference was not significant (16.0 vs 13.5 months; P = .13). OS was significantly improved for DE-Mth patients compared with HC-Mth (35.5 vs 23.3 months; P = .049) despite nonsignificant improvement in PFS (10.7 vs 9.0 months; P = .26). Grade 3 central nervous system necrosis occurred in 13% of patients, but treatment with bevacizumab improved symptoms in all cases. Conclusions 18F-DOPA PET–guided DERT appears to be safe, and it significantly improves PFS in MGMT unmethylated glioblastoma. OS is significantly improved in MGMT methylated patients. Further investigation of 18F-DOPA PET biologic guided DERT for glioblastoma is warranted.

Purpose Methylation of the O6-methylguanine methyltransferase (MGMT) gene promoter is associated with improved treatment response and survival in patients with glioblastoma (GB), but the necessary pathologic specimen can be nondiagnostic. In this study, we assessed whether radiomics features from pretreatment 18F-DOPA positron emission tomography (PET) imaging could be used to predict pathologic MGMT status. Methods and Materials This study included 86 patients with newly diagnosed GB, split into 3 groups (training, validating, and predicting). We performed a radiomics analysis on 18F-DOPA PET images by extracting features from 2 tumor-based contours: a “Gold” contour of all abnormal uptake per expert nuclear medicine physician and a high-grade glioma (HGG) contour based on a tumor-to-normal hemispheric ratio >2.0, representing the most aggressive components. Feature selection was performed by comparing the weighted feature importance and filtering with bivariate analysis. Optimization of model parameters was explored using grid search with selected features. The stability of the model with increasing input features was also investigated for model robustness. The model predictions were then applied by comparing the overall survival probability of the patients with GB and unknown MGMT status versus those with known MGMT status. Results A radiomics signature was constructed to predict MGMT methylation status. Using features extracted from HGG contour alone with a random forest model, we achieved 80% ± 10% accuracy for 95% confidence level in predicting MGMT status. The prediction accuracy was not improved with the addition of the Gold contour or with more input features. The model was applied to the patients with unknown MGMT methylation status. The prediction results are consistent with what is expected using overall survival as a surrogate. Conclusions This study suggests that 3 features from radiomics modeling of 18F-DOPA PET imaging can predict MGMT methylation status with reasonable accuracy. These results could provide valuable therapeutic guidance for patients in whom MGMT testing is inconclusive or nondiagnostic.

Prostate-specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with

PET imaging with β-amyloid ligands is emerging as a molecular imaging technique targeting white matter integrity and demyelination. β-amyloid PET ligands such as (11)C-Pittsburgh compound B ((11)C-PiB) have been considered for quantitative measurement of myelin content changes in multiple sclerosis, but (11)C-PiB is not commercially available given its short half-life. A (18)F PET ligand such as flutemetamol with a longer half-life may be an alternative, but its ability to differentiate white matter hyperintensities (WMH) from normal-appearing white matter (NAWM) and its relationship with age remains to be investigated. Methods: Cognitively unimpaired (CU) older and younger adults (n = 61) were recruited from the community responding to a study advertisement for β-amyloid PET. Participants prospectively underwent MRI, (11)C-PiB, and (18)F-flutemetamol PET scans. MRI fluid-attenuated inversion recovery images were segmented into WMH and NAWM and registered to the T1-weighted MRI. (11)C-PiB and (18)F-flutemetamol PET images were also registered to the T1-weighted MRI. (11)C-PiB and (18)F-flutemetamol SUV ratios (SUVrs) from the WMH and NAWM were calculated using cerebellar crus uptake as a reference for both (11)C-PiB and (18)F-flutemetamol. Results: The median age was 38 y (range, 30–48 y) in younger adults and 67 y (range, 61–83 y) in older adults. WMH and NAWM SUVrs were higher with (18)F-flutemetamol than with (11)C-PiB in both older (P < 0.001) and younger (P < 0.001) CU adults. (11)C-PiB and (18)F-flutemetamol SUVrs were higher in older than in younger CU adults in both WMH (P < 0.001) and NAWM (P < 0.001). (11)C-PiB and (18)F-flutemetamol SUVrs were higher in NAWM than WMH in both older (P < 0.001) and younger (P < 0.001) CU adults. There was no apparent difference between (11)C-PiB and (18)F-flutemetamol SUVrs in differentiating WMH from NAWM in older and in younger adults. Conclusion: (11)C-PiB and (18)F-flutemetamol show a similar topographic pattern of uptake in white matter with a similar association with age in WMH and NAWM. (11)C-PiB and (18)F-flutemetamol can also effectively distinguish between WMH and NAWM. However, given its longer half-life, commercial availability, and higher binding potential, (18)F-flutemetamol can be an alternative to (11)C-PiB in molecular imaging studies specifically targeting multiple sclerosis to evaluate white matter integrity.

Background The purpose of this study was to assess the impact of vendor-provided atlas-based MRAC on FDG PET/MR for the evaluation of Alzheimer’s disease (AD) by using simulated images. Methods We recruited 47 patients, from two institutions, who underwent PET/CT and PET/MR (GE SIGNA) examination for oncological staging. From the PET raw data acquired on PET/MR, two FDG-PET series were generated, using vendor-provided MRAC (atlas-based) and CTAC. The following simulation steps were performed in MNI space: After spatial normalization and smoothing of the PET datasets, we calculated the error map for each patient, PETMRAC/PETCTAC. We multiplied each of these 47 error maps with each of the 203 Alzheimer’s Disease Neuroimaging Initiative (ADNI) cases after the identical normalization and smoothing. This resulted in 203*47 = 9541 datasets. To evaluate the probability of AD in each resulting image, a cumulative t-value was calculated automatically using commercially-available software (PMOD PALZ) which has been used in multiple large cohort studies. The diagnostic accuracy for the discrimination of AD and predicting progression from mild cognitive impairment (MCI) to AD were evaluated in simulated images compared with ADNI original images. Results The accuracy and specificity for the discrimination of AD-patients from normal controls were not substantially impaired, but sensitivity was slightly impaired in 5 out of 47 datasets (original vs. error; 83.2% [CI 75.0%-89.0%], 83.3% [CI 74.2%-89.8%] and 83.1% [CI 75.6%-88.3%] vs. 82.7% [range 80.4–85.0%], 78.5% [range 72.9–83.3%,] and 86.1% [range 81.4–89.8%]). The accuracy, sensitivity and specificity for predicting progression from MCI to AD during 2-year follow-up was not impaired (original vs. error; 62.5% [CI 53.3%-69.3%], 78.8% [CI 65.4%-88.6%] and 54.0% [CI 47.0%-69.1%] vs. 64.8% [range 61.5–66.7%], 75.7% [range 66.7–81.8%,] and 59.0% [range 50.8–63.5%]). The worst 3 error maps show a tendency towards underestimation of PET scores. Conclusion FDG-PET/MR based on atlas-based MR attenuation correction showed similar diagnostic accuracy to the CT-based method for the diagnosis of AD and the prediction of progression of MCI to AD using commercially-available software, although with a minor reduction in sensitivity.

PURPOSE: Methylation of the O(6)-methylguanine methyltransferase (MGMT) gene promoter is associated with improved treatment response and survival in patients with Glioblastoma (GB), but the necessary pathological specimen can be non-diagnostic. In this study, we assessed whether radiomics features pre-treatment (18)F-DOPA PET imaging could be used to predict pathologic MGMT status. METHODS: This study included 86 patients with newly diagnosed GB, split into three groups (training, validating, predicting). We performed radiomics analysis on (18)F-DOPA PET images by extracting features two tumor-based contours: a “Gold” contour of all abnormal uptake per expert Nuclear Medicine physician, and an “HGG” contour based on a T/N > 20 representing the most aggressive components. Feature selection was performed by comparing the weighted feature importance and filtering with bivariate analysis. Optimization of model parameters was explored using grid search with selected features. The stability of the model with increasing input features was also investigated for model robustness. The model predictions were then applied by comparing the overall survival (OS) probability of the GB patients with unknown MGMT status vs those with known MGMT status. RESULTS: A radiomics signature was constructed to predict MGMT methylation status. Using features extracted HGG contour alone with a Random Forest model, we achieved 80% ± 10% accuracy for 95% confidence level in predicting MGMT status. The prediction accuracy was not improved with the addition of the Gold contour or with more input features. The model was applied to the patients with unknown MGMT methylation status. The prediction results are consistent with what is expected using OS as a surrogate. CONCLUSIONS: This study suggests that 3 features radiomics modeling of (18)F-DOPA PET imaging can predict the MGMT methylation status with reasonable accuracy. It may provide valuable therapeutic guidance for patients where MGMT testing is inconclusive or non-diagnostic.

Purpose The impact of MR-based attenuation correction on PET quantitation accuracy is an ongoing cause of concern for advanced brain research with PET/MR. The purpose of this study was to evaluate a new, template-enhanced zero-echo-time attenuation correction method for PET/MR scanners. Methods 30 subjects underwent a clinically-indicated 18F-FDG-PET/CT, followed by PET/MR on a GE SIGNA PET/MR. For each patient, a 42-s zero echo time (ZTE) sequence was used to generate two attenuation maps: one with the standard ZTE segmentation-based method; and another with a modification of the method, wherein pre-registered anatomical templates and CT data were used to enhance the segmentation. CT data, was used as gold standard. Reconstructed PET images were qualified visually and quantified in 68 volumes-of-interest using a standardized brain atlas. Results Attenuation maps were successfully generated in all cases, without manual intervention or parameter tuning. One patient was excluded from the quantitative analysis due to the presence of multiple brain metastases. The PET bias with template-enhanced ZTE attenuation correction was measured to be −0.9% ± 0.9%, compared with −1.4% ± 1.1% with regular ZTE attenuation correction. In terms of absolute bias, the new method yielded 1.1% ± 0.7%, compared with 1.6% ± 0.9% with regular ZTE. Statistically significant bias reduction was obtained in the frontal region (from −2.0% to −1.0%), temporal (from −1.2% to −0.2%), parietal (from −1.9% to −1.1%), occipital (from −2.0% to −1.1%) and insula (from −1.4% to −1.1%). Conclusion These results indicate that the co-registration of pre-recorded anatomical templates to ZTE data is feasible in clinical practice and can be effectively used to improve the performance of segmentation-based attenuation correction.

The purpose of this article is to provide an update on clinical PET/MRI, including current and developing clinical indications and technical developments.PET/MRI is evolving rapidly, transitioning from a predominant research focus to exciting clinical practice. Key technical obstacles have been overcome, and further technical advances promise to herald significant advancements in image quality. Further optimization of protocols to address challenges posed by this hybrid modality will ensure the long-term success of PET/MRI.

While dose escalation of radiotherapy (DERT) has failed to improve overall survival (OS) or progression-free survival (PFS) for glioblastoma in previous studies, a recent phase II clinical trial utilizing 18F-DOPA-PET-directed DERT demonstrated improved PFS in MGMT-unmethylated patients and OS in MGMT-methylated patients compared to historical controls. This planned secondary analysis sought to determine 1) how 18F-DOPA-PET changes RT volumes beyond standard MRI-planning, 2) which patients benefit most and least from this protocol, 3) which are mostly likely to experience clinically significant radionecrosis after DERT, and 4) patterns of failure after DERT. For 69 evaluable patients, median MRI-defined, PET-defined, and combined low-dose gross tumor volumes (GTV51) were 54 cc (range 9-248), 23 cc (0.4-179), and 62 cc (10-260), respectively. Median MRI-defined, PET-defined, and combined high-dose GTVs (GTV76) were 32 cc (range 4-136), 6 cc (0.1-138), and 34 cc (4-162), respectively. 18F-DOPA-PET resulted in a median volumetric expansion of 13% (0-243%) and 5% (0-217%) from MRI-defined low-dose and high-dose GTV’s, respectively. Central failures ( >95% of recurrence tumor volume) occurred within the 76 Gy, 60 Gy, and 51 Gy isodose lines in 32 (46%), 60 (87%), and 64 (93%) patients, respectively. Recursive partitioning analysis stratified patients by OS and PFS. Patients with 18F-DOPA-PET-defined GTV76 > 7.8cc, MRI-defined GTV76 > 42.7cc, and MGMT promotor-unmethylated tumors had the shortest OS, while patients with smaller PET and MRI-defined tumors had the longest OS (median 10.4 vs. 64.6 months, p< 0.001). Similarly, PFS was worst in patients with 18F-DOPA-PET-defined GTV76 > 2.17 cc who had biopsy only (median PFS 3.2 months, p< 0.001). Patients with 18F-DOPA-PET-defined GTV51 > 50 cc had the highest risk of grade 3+ radionecrosis (p< 0.001). In conclusion, larger 18F-DOPA-PET and MRI-defined tumor volumes were associated with worse outcomes, and 18F-DOPA-PET-directed DERT appears to reduce risk of central recurrence in high-dose volumes.

Background 18F-Tetrafluoroborate (18F-TFB) is a promising iodide analog for PET imaging of thyroid cancer and sodium/iodide symporter (NIS) reporter activity in viral therapy applications. The aim of this study was to evaluate the safety, pharmacokinetics, biodistribution, and radiation dosimetry of high-specific activity 18F-TFB in healthy human subjects. Methods 18F-TFB was synthesized with specific activity of 3.2 ± 1.3 GBq/μmol (at the end of synthesis). Dynamic and whole-body static PET/CT scans over 4 h were performed after intravenous administration of 18F-TFB (333–407 MBq) in four female and four male healthy volunteers (35 ± 11 years old). Samples of venous blood and urine were collected over the imaging period and analyzed by ion-chromatography HPLC to determine tracer stability. Vital signs and clinical laboratory safety assays were measured to evaluate safety. Results 18F-TFB administration was well tolerated with no significant findings on vital signs and no clinically meaningful changes in clinical laboratory assays. Left-ventricular blood pool time-activity curves showed a multi-phasic blood clearance of 18F-radioactivity with the two rapid clearance phases over the first 20 min, followed by a slower clearance phase. HPLC analysis showed insignificant 18F-labeled metabolites in the blood and urine over the length of the study (4 h). High uptakes were seen in the thyroid, stomach, salivary glands, and bladder. Urinary clearance of 18F-TFB was prominent. Metabolic stability was evidenced by low accumulation of 18F-radioactivity in the bone. Effective doses were 0.036 mSv/MBq in males and 0.064 mSv/MBq in females (p = 0.08, not significant). Conclusions This initial study in healthy human subjects showed 18F-TFB was safe and distributed in the human body similar to other iodide analogs. These data support further translational studies with 18F-TFB as NIS gene reporter and imaging biomarker for thyroid cancer and other disease processes that import iodide. Electronic supplementary material The online version of this article (10.1186/s13550-017-0337-5) contains supplementary material, which is available to authorized users.

Quantitative measurements of change in β-amyloid load from Positron Emission Tomography (PET) images play a critical role in clinical trials and longitudinal observational studies of Alzheimer's disease. These measurements are strongly affected by methodological differences between implementations, including choice of reference region and use of partial volume correction, but there is a lack of consensus for an optimal method. Previous works have examined some relevant variables under varying criteria, but interactions between them prevent choosing a method via combined meta-analysis. In this work, we present a thorough comparison of methods to measure change in β-amyloid over time using Pittsburgh Compound B (PiB) PET imaging. Methods We compare 1,024 different automated software pipeline implementations with varying methodological choices according to four quality metrics calculated over three-timepoint longitudinal trajectories of 129 subjects: reliability (straightness/variance); plausibility (lack of negative slopes); ability to predict accumulator/non-accumulator status from baseline value; and correlation between change in β-amyloid and change in Mini Mental State Exam (MMSE) scores. Results and conclusion From this analysis, we show that an optimal longitudinal measure of β-amyloid from PiB should use a reference region that includes a combination of voxels in the supratentorial white matter and those in the whole cerebellum, measured using two-class partial volume correction in the voxel space of each subject's corresponding anatomical MR image.

Background Understanding the variation in uptake between different amyloid PET tracers is important to appropriately interpret data using different amyloid tracers. Therefore, we compared the uptake differences in [ 18 F]Flutemetamol (FMT) and [ 11 C]PiB (PiB) PET in the same people. Methods Structural MRI, FMT PET and PiB PET were each performed in 30 young cognitively normal (yCN), 31 elderly cognitively normal (eCN) and 21 Alzheimer's disease dementia (AD) participants. PiB and FMT images for each participant were compared quantitatively using voxel- and region-based analyses. Region of interest (ROI) analyses included comparisons of grey matter (GM) regions as well as white matter (WM) regions. Regional comparisons of each tracer between different groups and comparisons of the two modalities within the different groups were performed. To compare mean SUVr between modalities, and between diagnostic groups, we used paired t -tests and Student's t -test, respectively. We also compared the ability of the two tracers to discriminate between diagnostic groups using AUROC estimates. The effect of using different normalization regions on SUVr values was also evaluated. Results Both FMT and PiB showed greater uptake throughout GM structures in AD vs. eCN or yCN. In all dual-modality group comparisons (FMT vs. PiB in yCN, eCN, and AD), greater WM uptake was seen with FMT vs. PiB. In yCN and eCN greater diffuse GM uptake was seen with FMT vs. PiB. When comparing yCN to eCN within each tracer, greater WM uptake was seen in eCN vs yCN. Conclusions Flutemetamol and PiB show similar topographical GM uptake in AD and CN participants and the tracers show comparable group discrimination. Greater WM accumulation with FMT suggests that quantitative differences vs. PiB will be apparent when using WM or GM as a reference region. Both imaging tracers demonstrate increased WM uptake in older people. These findings suggest that using different amyloid tracers or different methods of analyses in serial brain imaging in an individual may result in artifactual amyloid change measurements. Clinical use of several amyloid tracers in the same patient will have challenges that need to be carefully considered.

Introduction Tau-positron emission tomography (PET) imaging with AV1451 is sensitive to Alzheimer disease (AD)–related tau deposition in the brain. We (1) examined regional variation of average tau-PET standardized uptake value ratios (SUVRs) in a young normal population (30–49 years) and corrected for the regional variability and (2) tested if the standardized values (z-scores) scaled appropriately to capture regional Alzheimer-specific (i.e., amyloid sensitive) tau-PET changes in individuals aged 50+ years. Methods We identified 490 individuals (70 between 30–49 years as a reference group and 420 cognitively normal between 50–95 years of age) with tau-PET and amyloid PET scans from the Mayo Clinic Study of Aging. Results There was intrinsic regional variability in average tau-PET SUVR with uptakes higher in some regions than others, even in the younger individuals who would have minimal or no neurofibrillary tangles. We corrected for this using region of interest–specific z-scores based on the reference group. Amyloid and tau-PET uptake were associated throughout the brain after adjusting for age, with the highest correlations in the medial temporal regions. Discussion Regions with high-average SUVR are not necessarily those with the greatest tau pathology. Standardization is therefore recommended. Standardization of the data “realigns” the data such that the regional tau z-scores are informative of the disease process, that is, regions with high z-scores now coincide with regions correlated with amyloid deposition. Medial temporal structures, specifically entorhinal cortex–tau, may be useful as an AD-specific tau-PET signature due to its sensitivity to amyloid.

Background:The role of coronary microvascular disease and its impact on functional and energetic reserve in heart failure with preserved ejection fraction (HFpEF) remains unclear. We hypothesized that in response to submaximal pharmacologic stress (dobutamine), patients with HFpEF have impairment in left ventricular (LV) myocardial mechanical (external work [EW]), energetic (myocardial O2consumption [MVO2]), and myocardial blood flow (MBF) reserve. We further assessed whether coupling of MBF to EW is impaired in HFpEF and associated with compensatory increases or pathological decreases in myocardial O2extraction. Lastly, we assessed whether coupling of MVO2to EW (mechanical efficiency) was impaired in HFpEF.Methods and Results:In prospectively enrolled patients with HFpEF (n=19) and age/sex-matched healthy controls (n=19), we performed11C-acetate positron emission tomography assessing MVO2and MBF at rest and during dobutamine infusion. EW was calculated as stroke volume (echo)×end-systolic pressure×heart rate. At rest, compared with controls, patients with HFpEF had higher LV EW, MVO2, and MBF. With dobutamine, LV EW, MVO2, and MBF increased in both HFpEF and controls; however, the magnitude of increases was significantly smaller in HFpEF. In both groups, MBF increased in relation to EW, but in HFpEF, the slope of the relationship was significantly smaller than in controls. Myocardial O2extraction was increased in HFpEF. Mechanical efficiency was similar in HFpEF and controls. In a post hoc analysis, HFpEF patients with LV hypertrophy (n=10) had significant reductions in LV mechanical efficiency relative to controls.Conclusions:In HFpEF during submaximal dobutamine stress, there is myocardial mechanical-, energetic- and flow-reserve dysfunction with impaired coupling of blood flow to demand and slight increases in myocardial O2extraction. These findings provide evidence that coronary microvascular dysfunction is present in HFpEF, limits O2supply relative to demand, and is associated with reserve dysfunction.

Positron emission tomography (PET) radiopharmaceuticals can noninvasively measure free fatty acid (FFA) uptake into adipose tissue. We studied 29 volunteers to test whether abdominal and femoral subcutaneous adipose tissue FFA uptake measured using [1-11C]palmitate PET agrees with FFA storage rates measured using an intravenous bolus of [1-14C]palmitate and adipose biopsies. The dynamic left ventricular cavity PET images combined with blood sample radioactivity corrected for the 11CO2 content were used to create the blood time activity curve (TAC), and the constant ( Ki) was determined using Patlak analysis of the TACs generated for regions of interest in abdominal subcutaneous fat. These data were used to calculate palmitate uptake rates in abdominal subcutaneous adipose tissue (µmol·kg−1·min−1). Immediately after the dynamic imaging, a static image of the thigh was taken to measure the standardized uptake value (SUV) in thigh adipose tissue, which was scaled to each participant’s abdominal adipose tissue SUV to calculate thigh adipose palmitate uptake rates. Abdominal adipose palmitate uptake using PET [1-11C]palmitate was correlated with, but significantly ( P < 0.001) greater than, FFA storage measured using [1-14C]palmitate and adipose biopsy. Thigh adipose palmitate measured using PET calculation was positively correlated ( R2 = 0.44, P < 0.0001) with and not different from the biopsy approach. The relative differences between PET measured abdominal subcutaneous adipose tissue palmitate uptake and biopsy-measured palmitate storage were positively correlated ( P = 0.03) with abdominal subcutaneous fat. We conclude that abdominal adipose tissue FFA uptake measured using PET does not equate to adipose FFA storage measured using biopsy techniques.

Introduction A standardised method for quantifying β-amyloid PET tracers would allow comparison across different tracers and different sites. The development of the Centiloid scale has aimed to achieve this, applying a common scale to better aid the diagnosis and prognosis of Alzheimer’s disease (AD) and to monitor anti-amyloid therapeutic interventions. Here, we apply the Centiloid method to [18F]flutemetamol and [11C]PiB (PiB, Pittsburgh compound B) PET images and derive the scaling factor to express their binding in Centiloids. Methods Paired PiB and [18F]flutemetamol scans for 74 subjects, including 24 young healthy controls (37 ± 5 years), were analysed using the standard Centiloid method. The same subjects were also analysed using PMOD- and FSL-based pipelines as well as SPM8. Test-retest analysis of 10 AD subjects was also performed with each pipeline. Results The standard uptake value ratios (SUVR), determined using the standard SPM8 Centiloid process, showed a strong correlation between [18F]flutemetamol (Flute) and PiB binding (SUVR-Flute = 0.77 × SUVR-PiB + 0.22, R 2 = 0.96). Application of the standard Centiloid process allowed the calculation of a direct conversion equation for SUVR-Flute to Centiloid units (CL) (CL = (121.42*SUVR-Flute) − 121.16). Analysis of the data via the two alternate Centiloid pipelines allowed us to derive standardised, SPM8-equivalent equations for both PMOD (CL = (115.24*SUVR-Flute) − 107.86) and FSL (CL = (120.32*SUVR-Flute) − 112.75) respectively. Test-retest analysis of 10 AD subjects showed an approximate 2% difference for each pipeline. Conclusions [18F]flutemetamol data can now be expressed in Centiloid units, enhancing its utility in clinical and research applications for β-amyloid imaging. The standard Centiloid method also demonstrates that [18F]flutemetamol has favourable performance compared with PiB and other β-amyloid tracers. Test-retest difference averaged 2%, with no difference between image processing pipelines. Centiloid scaling is robust and can be implemented on a number of platforms.

Treatment-related changes can be difficult to differentiate from progressive glioma using MRI with contrast (CE). The purpose of this study is to compare the sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical planning. Stereotactic biopsies were obtained from regions of concordant and discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity. The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on histopathologic analysis. Receiver operating characteristic curve analysis revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F-DOPA-PET avidity (P+). Imaging characteristics included M−P− in 16%, M−P+ in 32%, M+P+ in 46% and M+P− in 5%. Histopathologic review of biopsies revealed grade II components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased sensitivity and specificity compared with MRI CE for visualizing the spatial distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET into re-irradiation target volume delineation for RT planning.

Treadmill exercise nitrogen-13 ((13)N)-ammonia positron emission tomography (PET) has logistical challenges and limited literature. We aimed to assess its feasibility, image quality, and diagnostic accuracy in obese and nonobese patients.Between 2009 and 2012, 10,804 patients were referred for myocardial perfusion imaging, including 300 for treadmill PET, of whom 265 were included in this study. Treadmill testing and PET were performed using standard procedures. Image quality, perfusion, and summed stress score (SSS) were assessed. Invasive coronary angiography was performed within 90 days of PET in 43 patients. Mean ± SD body mass index (BMI) was 35.7 ± 7.7 kg/m(2) (range 19.5-63.5 kg/m(2)). Feasibility of treadmill (13)N-ammonia PET was 100%. Exercise duration was less for obese patients than nonobese patients (P .001). Image quality was rated good for 96.9% of obese and 100% of nonobese patients. For all patients, sensitivity was 86.4% and specificity was 74.4%. Diagnostic accuracy did not change significantly with increasing BMI. SSS remained significant in predicting angiographic coronary artery disease after adjustment for age, sex, and Duke treadmill score.Treadmill (13)N-ammonia PET is highly feasible, yields good image quality, and has moderately high diagnostic accuracy in a small subset of obese and nonobese patients who are deemed able to perform treadmill exercise.

The advances in PET scanning for thoracic diseases that are deemed most likely to have clinical impact in the near-term future are highlighted in this article. We predict that the current practice of medicine will continue to embrace the power of molecular imaging and specifically PET scanning. 18F-fluorodeoxyglucose-PET scanning will continue to evolve and will expand into imaging of inflammatory disorders. New clinically available PET scan radiotracers, such as PET scan versions of octreotide and amyloid imaging agents, will expand PET imaging into different disease processes. Major improvements in thoracic PET/CT imaging technology will become available, including fully digital silicone photomultipliers and Bayesian penalized likelihood image reconstruction. These will result in significant improvements in image quality, improving the evaluation of smaller lung nodules and metastases and allowing better prediction of prognosis. The birth of clinical PET/MRI scan will add new imaging opportunities, such as better PET imaging of pleural diseases currently obscured by complex patient motion.

PET radiopharmaceuticals can noninvasively measure free fatty acid (FFA) tissue uptake. Investigators often use PET scan-derived data to calculate FFA flux. We tested whether the [1-11C]palmitate PET measures of palmitate flux provide results equivalent to a continuous infusion of [U-13C]palmitate. Nine volunteers participated in study 1 to evaluate whether a rapidly (10–20 s) given bolus of [1-11C]palmitate affects calculated flux results. Thirty volunteers participated in study 2, which was identical to study 1 except that the [1-11C]palmitate bolus was given over 1 min. Volunteers in both studies also received a continuous intravenous infusion of [U-13C]palmitate. Plasma palmitate concentrations and enrichment were measured by liquid chromatography-mass spectrometry. The PET/CT images were analyzed on a workstation running PMOD. Palmitate flux was estimated using PET time-activity curve (TAC) data from regions of interest in the left ventricle (LV) and aorta both with and without hybrid TACs that employed the11CO2-corrected data for the first 5 min and the11CO2-corrected blood radioactivity for the remainder of the PET scan. Palmitate flux in study 1 measured with PET [1-11C]palmitate and [U-13C]palmitate were not correlated, and the PET [1-11C]palmitate flux was significantly less than the [U-13C]palmitate measured flux. In study 2, the palmitate flux using PET [1-11C]palmitate hybrid LV models provided closer mean estimates of [U-13C]palmitate measured flux. The best PET calculation approaches predicted 64% of the interindividual variance in [U-13C]palmitate measured flux. Palmitate kinetics measured using [1-11C]palmitate/PET do not provide the same palmitate kinetic results as the continuous infusion [U-13C]palmitate approach.

Background Understanding the variation in uptake between different amyloid PET tracers is important to appropriately interpret data using different amyloid tracers. Therefore, we compared the uptake differences in [18F]Flutemetamol (FMT) and [11C]PiB (PiB) PET in the same people. Methods Structural MRI, FMT PET and PiB PET were each performed in 30 young cognitively normal (yCN), 31 elderly cognitively normal (eCN) and 21 Alzheimer's disease dementia (AD) participants. PiB and FMT images for each participant were compared quantitatively using voxel- and region-based analyses. Region of interest (ROI) analyses included comparisons of grey matter (GM) regions as well as white matter (WM) regions. Regional comparisons of each tracer between different groups and comparisons of the two modalities within the different groups were performed. To compare mean SUVr between modalities, and between diagnostic groups, we used paired t-tests and Student's t-test, respectively. We also compared the ability of the two tracers to discriminate between diagnostic groups using AUROC estimates. The effect of using different normalization regions on SUVr values was also evaluated. Results Both FMT and PiB showed greater uptake throughout GM structures in AD vs. eCN or yCN. In all dual-modality group comparisons (FMT vs. PiB in yCN, eCN, and AD), greater WM uptake was seen with FMT vs. PiB. In yCN and eCN greater diffuse GM uptake was seen with FMT vs. PiB. When comparing yCN to eCN within each tracer, greater WM uptake was seen in eCN vs yCN. Conclusions Flutemetamol and PiB show similar topographical GM uptake in AD and CN participants and the tracers show comparable group discrimination. Greater WM accumulation with FMT suggests that quantitative differences vs. PiB will be apparent when using WM or GM as a reference region. Both imaging tracers demonstrate increased WM uptake in older people. These findings suggest that using different amyloid tracers or different methods of analyses in serial brain imaging in an individual may result in artifactual amyloid change measurements. Clinical use of several amyloid tracers in the same patient will have challenges that need to be carefully considered., Highlights • White matter uptake is quantitatively elevated in elderly vs. younger control subjects in both FMT and PiB PET scans. • Quantitatively greater white matter uptake is seen in FMT vs. PiB in Alzheimer’s disease dementia and control subjects. • Variations between FMT and PiB may create the false appearance of changing brain amyloid levels on serial imaging. • FMT and PiB have comparable ability to categorize Alzheimer’s disease dementia and control subjects cross-sectionally. • Methods to cross-calibrate different amyloid PET tracers will need to be validated in serial imaging paradigms.

Animal models have demonstrated that CD36 facilitates cell membrane free fatty acid (FFA) transport, but its role in human metabolism is not well understood. We measured heart, liver, adipose (three depots), and muscle (truncal postural and thigh locomotive) FFA uptake using [11C]palmitate positron emission tomography (PET) scans in a family of five carrying the Pro90Ser CD36 mutation (2 homozygotes had no CD36) and matched control volunteers. PET scans were done under conditions of suppressed and slightly increased palmitate concentrations. During suppressed palmitate conditions, muscle and adipose palmitate uptake were markedly reduced in homozygotes but not heterozygotes for the Pro90Ser CD36 mutation, whereas when palmitate concentration was slightly increased, uptake in muscle and adipose did not differ between control subjects and homozygous family members. Hepatic FFA uptake was similar in all participants regardless of palmitate concentrations, whereas myocardial FFA uptake was diminished in the Pro90Ser homozygotes during both suppressed and increased palmitate conditions. We conclude that CD36 1) facilitates FFA transport into muscle and adipose tissue in humans when extracellular concentrations are reduced but not when they are modestly elevated, 2) is not rate limiting for hepatic FFA uptake, and 3) is needed for normal cardiac FFA uptake over a range of FFA concentrations from low to slightly elevated.

We have previously described an automated system for the co-registration of PiB and FDG PET images with structural MRI and a neurological anatomy atlas to produce region-specific quantization of cortical activity and amyloid burden. We also reported a global joint PiB/FDG histogram-based measure (FDG-Associated PiB Uptake Ratio – FAPUR) that performed as well as regional PiB ratio in stratifying Alzheimer’s disease (AD) and Lewy Body Dementia (LBD) patients from normal subjects in an autopsy-verified cohort of 31. In this paper we examine results of this analysis on a clinically-verified cohort of 718 normal volunteers. We found that the global FDG ratio correlated negatively with age (r2 = 0.044) and global PiB ratio correlated positively with age (r2=0.038). FAPUR also correlated negatively with age (r2-.025), and in addition, we introduce a new metric – the Pearson’s correlation coefficient (r2) of the joint PiB/FDG histogram which correlates positively (r2=0.014) with age. We then used these measurements to construct age-weighted Z-scores for all measurements made on the original autopsy cohort. We found similar stratification using Z-scores compared to raw values; however, the joint PiB/FDG r2 Z-score showed the greatest stratification ability.

Background— The objective of the present study was to investigate the effect of cardiac resynchronization therapy (CRT) on cardiac autonomic function. Methods and Results— This prospective study included 45 consecutive patients with heart failure who received CRT devices with defibrillator and 20 age-matched, healthy control subjects. At baseline and 3 months and 6 months after CRT, we assessed New York Heart Association (NYHA) class, 6-minute walk distance, plasma sympathetic biomarker nerve growth factor, echocardiography, heart rate variability and cardiac presynaptic sympathetic function determined by iodine 123 metaiodobenzylguanidine scintigraphy. After CRT, NYHA class improved by 1 class ( P P P =0.004) and the standard deviation of the averaged normal-to-normal R-R intervals (82.62±23.03 ms versus 100.50±34.87 ms; P =0.004), the delayed heart/mediastinum (H/M) ratio increased (1.82 [0.58] versus 1.97 [0.59]; P =0.03), whereas the mean (SD) H/M washout rate was reduced (48% [19%] versus 37% [22%]; P =0.01). Twenty-two of 45 study patients responded to CRT, with a reduction of left ventricular end-systolic volume index >15%. Compared with nonresponders, responders had a higher delayed H/M ratio (2.11 versus 1.48; P =0.003) and lower H/M washout rate (37% versus 62%; P =0.003) at baseline. Conclusions— CRT improved sympathetic function. Cardiac sympathetic reserve may be a marker for the reversibility of failing myocardial function.

Our objectives were to, first, determine the oncolytic potential of an engineered measles virus expressing the sodium-iodide symporter gene (MV-NIS) for intratumoral (i.t.) therapy of pancreatic cancer and, second, evaluate NIS as a reporter gene for in vivo monitoring and quantitation of MV-NIS delivery, viral spread, and gene expression in this tumor model.Cultured human pancreatic cancer cells were infected with MV-NIS. Light microscopy, cell viability, and iodide uptake assays were used to confirm viral infection and NIS gene expression and function in vitro. Human pancreatic tumor xenografts were established in mice and infected via i.t. MV-NIS injections. NIS-mediated i.t. iodide uptake was quantitated by (123)I micro-SPECT/CT. i.t. MV-NIS infection was confirmed by immunohistochemistry of excised pancreatic xenografts. The oncolytic efficacy of MV-NIS was determined by measurement of tumor growth and mouse survival.Infection of human pancreatic cancer cell lines with MV-NIS in vitro resulted in syncytia formation, marked iodide uptake, and ultimately cell death. Tumor xenografts infected with MV-NIS concentrated radioiodine, allowing serial quantitative imaging with (123)I micro-SPECT/CT. i.t. MV-NIS therapy of human pancreatic cancer xenografts resulted in a significant reduction in tumor volume and increased survival time of the treated mice compared with the control mice.MV-NIS efficiently infects human pancreatic tumor cells and results in sufficient radioiodine uptake to enable noninvasive serial imaging and quantitation of the intensity, distribution, and time course of NIS gene expression. MV-NIS also shows oncolytic activity in human pancreatic cancer xenografts: Tumor growth is reduced and survival is increased in mice treated with the virus.

PET scanners are designed to function over a wide dynamic range of imaging conditions. Clinical constraints, such as injected activity and imaging time, often limit the realization of optimal system capability. The ‘working range’ of image quality for a given imaging situation is dictated by a trade-off of signal to noise. By adjusting scan time and reconstruction parameters, an acceptable trade-off is fixed into a protocol. This study develops the use of quantitative measures using hot and cold rods inserts in head and body-sized phantoms to quantitatively and visually assess two different PET scanner geometries and multiple reconstruction methods in order to further understand optimal scanner design and use in different imaging conditions.

This study was undertaken to determine the ability of micro-single photon emission computed tomography (micro-SPECT)/computed tomography (CT) to accurately quantitate intratumoral radioisotope uptake in vivo and to compare these measurements with planar imaging and micro-SPECT imaging alone. Human pancreatic cancer xenografts were established in 10 mice. Intratumoral radioisotope uptake was achieved via intratumoral injection of an attenuated measles virus vector expressing the NIS gene (MV-NIS). On various days after MV-NIS injection, 123I planar and micro-SPECT/CT imaging was performed. Tumor activity was determined by dose calibrator measurements and region-of-interest (ROI) image analysis. Agreement and reproducibility of tumor activity measurements were assessed by Bland–Altman plots and Lin’s concordance correlation coefficient (CCC). Intratumoral radioisotope uptake was detected in all mice. Scatterplots demonstrate strong agreement (CCC = 0.93) between micro-SPECT/CT ROI image analysis and dose calibrator tumor activity measurements. The differences between dose calibrator activity measurements and those obtained with ROI image analysis of micro-SPECT alone and planar imaging are less accurate and more variable (CCC = 0.84 and 0.78, respectively). Micro-SPECT/CT can be used to accurately quantify intratumoral radioisotope uptake in vivo and is more reliable than planar or micro-SPECT imaging alone.

A complex analysis performed by spatial registration of PiB and MRI patient images in order to localize the PiB signal to specific cortical brain regions has been proven effective in identifying imaging characteristics associated with underlying Alzheimer’s Disease (AD) and Lewy Body Disease (LBD) pathology. This paper presents an original method of image analysis and stratification of amyloid-related brain disease based on the global spatial correlation of PiB PET images with 18F-FDG PET images (without MR images) to categorize the PiB signal arising from the cortex. Rigid registration of PiB and 18F-FDG images is relatively straightforward, and in registration the 18F-FDG signal serves to identify the cortical region in which the PiB signal is relevant. Cortical grey matter demonstrates the highest levels of amyloid accumulation and therefore the greatest PiB signal related to amyloid pathology. The highest intensity voxels in the 18F-FDG image are attributed to the cortical grey matter. The correlation of the highest intensity PiB voxels with the highest 18F-FDG values indicates the presence of β-amyloid protein in the cortex in disease states, while correlation of the highest intensity PiB voxels with mid-range 18F-FDG values indicates only nonspecific binding in the white matter.

We used the systems engineering technique of discrete event simulation modeling to assist in increasing patient access to positron emission tomographic examinations in the Department of Nuclear Medicine at Mayo Clinic, Rochester. The model was used to determine the best universal slot length to address the specific access challenges of a destination medical center such as Mayo Clinic. On the basis of the modeling, a new schedule was implemented in April 2012 and our before and after data analysis shows an increase of 2.4 scans per day. This was achieved without requiring additional resources or negatively affecting patient waiting, staff satisfaction (as evaluated by day length), or examination quality.

The cholangiopathies are a diverse group of biliary tract disorders, many of which lack effective treatment. Murine models are an important tool for studying their pathogenesis, but existing noninvasive methods for assessing biliary disease in vivo are not optimal. Here we report our experience with using micro-computed tomography (microCT) and nuclear magnetic resonance (MR) imaging to develop a technique for live-mouse cholangiography. Using mdr2 knockout (mdr2KO, a model for primary sclerosing cholangitis (PSC)), bile duct-ligated (BDL), and normal mice, we performed in vivo: (1) microCT on a Siemens Inveon PET/CT scanner and (2) MR on a Bruker Avance 16.4 T spectrometer, using Turbo Rapid Acquisition with Relaxation Enhancement, IntraGate Fast Low Angle Shot, and Half-Fourier Acquisition Single-shot Turbo Spin Echo methods. Anesthesia was with 1.5–2.5% isoflurane. Scans were performed with and without contrast agents (iodipamide meglumine (microCT), gadoxetate disodium (MR)). Dissection and liver histology were performed for validation. With microCT, only the gallbladder and extrahepatic bile ducts were visualized despite attempts to optimize timing, route, and dose of contrast. With MR, the gallbladder, extra-, and intrahepatic bile ducts were well-visualized in mdr2KO mice; the cholangiographic appearance was similar to that of PSC (eg, multifocal strictures) and could be improved with contrast administration. In BDL mice, MR revealed cholangiographically distinct progressive dilation of the biliary tree without ductal irregularity. In normal mice, MR allowed visualization of the gallbladder and extrahepatic ducts, but only marginal visualization of the diminutive intrahepatic ducts. One mouse died during microCT and MR imaging, respectively. Both microCT and MR scans could be obtained in ≤20 min. We, therefore, demonstrate that MR cholangiography can be a useful tool for longitudinal studies of the biliary tree in live mice, whereas microCT yields suboptimal duct visualization despite requiring contrast administration. These findings support further development and application of MR cholangiography to the study of mouse models of PSC and other cholangiopathies.

Digital radiography, CT, PET, and MR are complicated imaging modalities which are composed of many hardware and software components. These components work together in a highly coordinated chain of events with the intent to produce high quality images. Acquisition, processing and reconstruction of data must occur in a precise way for optimum image quality to be achieved. Any error or unexpected event in the entire process can produce unwanted pixel intensities in the final images which may contribute to visible image artifacts. The diagnostic imaging physicist is uniquely qualified to investigate and contribute to resolution of image artifacts. This course will teach the participant to identify common artifacts found clinically in digital radiography, CT, PET, and MR, to determine the causes of artifacts, and to make recommendations for how to resolve artifacts. Learning Objectives: 1.Identify common artifacts found clinically in digital radiography, CT, PET and MR. 2.Determine causes of various clinical artifacts from digital radiography, CT, PET and MR. 3.Describe how to resolve various clinical artifacts from digital radiography, CT, PET and MR.

Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. Dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63Zn-zinc citrate (∼330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63Zn clearances were compared with 11C-Pittsburgh Compound B (11C-PiB) and 18F-fluorodeoxyglucose (18F-FDG) imaging data. 63Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden (11C-PiB) and 18F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-β pathology, warranting further imaging studies of zinc homeostasis in patients with AD.

Background: We prospectively compared FLT-PET and FDG-PET in evaluating response to cetuximab and chemoradiotherapy for HNSCC. Methods: Six patients with HNSCC received cetuximab followed by chemoradiotherapy. Patients had FLTand FDG-PET scans at baseline, after cetuximab, and 2 weeks into chemoradiotherapy. Changes in SUVmax on successive scans were compared to baseline. Results: After induction therapy, changes in SUVmax ranged from -2 to 32% for FLT-PET and -24 to 0% for FDGPET. After two weeks of chemoradiotherapy, changes in SUVmax ranged from -71 to 9% for FLT-PET and -80 to -7% for FDG-PET. One patient experienced consecutive increases in FLT uptake not detected by FDG-PET. No patient recurred at a median 14.6 months. Conclusions: Functional imaging early during definitive therapy for HNSCC is feasible. Similar changes in FLT and FDG uptake are detected during chemoradiotherapy; however, distinct differences were seen after induction cetuximab therapy. Further follow-up will facilitate correlation of radiotracer uptake with clinical outcome.

BACKGROUND AND PURPOSE: Decreased glucose metabolism in the temporal and parietal lobes on FDG-PET is recognized as an early imaging marker for the AD pathology. Our objective was to investigate the effects of age on FDG-PET findings in aMCI. MATERIALS AND METHODS: Twenty-five patients with aMCI at 55–86 years of age (median = 73 years) and 25 age- and sex-matched CN subjects underwent FDG-PET. SPM5 was used to compare the FDG uptake in patients in aMCI-old (>73 years) and aMCI-young (≤73 years) groups with CN subjects. The findings in the aMCI-old patients were independently validated in a separate cohort of 10 aMCI and 13 CN subjects older than 73 years of age. RESULTS: The pattern of decreased glucose metabolism and gray matter atrophy in the medial temporal, posterior cingulate, precuneus, lateral parietal, and temporal lobes in aMCI-young subjects was consistent with the typical pattern observed in AD. The pattern of glucose metabolic changes in aMCI-old subjects was different, predominantly involving the frontal lobes and the left parietal lobe. Gray matter atrophy in aMCI-old subjects was less pronounced than that in the aMCI-young subjects, involving the hippocampus and the basal forebrain in both hemispheres CONCLUSIONS: Pathologic heterogeneity may be underlying the absence of AD-like glucose metabolic changes in older compared with younger patients with aMCI. This may be an important consideration for the clinical use of temporoparietal hypometabolism on FDG-PET as a marker for early diagnosis of AD in aMCI.

The purpose of this study was to compare the diagnostic accuracy of glucose metabolism and amyloid deposition as demonstrated by (18)F-FDG and Pittsburg Compound B (PiB) PET to evaluate subjects with cognitive impairment.Subjects were selected from existing participants in the Mayo Alzheimer's Disease Research Center or Alzheimer's Disease Patient Registry programs. A total of 20 healthy controls and 17 amnestic mild cognitive impairment (aMCI), 6 nonamnestic mild cognitive impairment (naMCI), and 13 Alzheimer disease (AD) subjects were imaged with both PiB and (18)F-FDG PET between March 2006 and August 2007. Global measures for PiB and (18)F-FDG PET uptake, normalized to cerebellum for PiB and pons for (18)F-FDG, were compared. Partial-volume correction, standardized uptake value (SUV), and cortical ratio methods of image analysis were also evaluated in an attempt to optimize the analysis for each test.Significant discrimination (P0.05) between controls and AD, naMCI and aMCI, naMCI and AD, and aMCI and AD by PiB PET measurements was observed. The paired groupwise comparisons of the global measures demonstrated that PiB PET versus (18)F-FDG PET showed similar significant group separation, with only PiB showing significant separation of naMCI and aMCI subjects.PiB PET and (18)F-FDG PET have similar diagnostic accuracy in early cognitive impairment. However, significantly better group discrimination in naMCI and aMCI subjects by PiB, compared with (18)F-FDG, was seen and may suggest early amyloid deposition before cerebral metabolic disruption in this group.

Patients with chronic calorie insufficiency commonly suffer from upper gastrointestinal dysfunction and consequent dyspeptic symptoms, which may interfere with their nutritional rehabilitation. To investigate the relationship between gastric dysfunction and feeding behavior, we exposed mice to chronic caloric restriction and demonstrated gastric motor abnormalities in them. Gastric dysmotility is typically associated with dyspeptic symptoms but sensations cannot be directly assessed in animal models. Therefore, as an initial step toward establishing measurable correlates of postprandial symptoms in small animals, we have attempted to characterize central responses to food intake by positron emission tomography-computerized microtomography (PET-CT) in normal and calorically restricted mice. Animals consumed a standard test meal after an overnight fast before receiving 2-deoxy-2[18F]fluoro-D-glucose tracer. The same mice were also scanned in the fasting state on a separate day. We were able to bring the fed and fasting PET volume images into spatial registration with each other and with an MR-derived atlas of the mouse brain, so that the differences in uptake between the two states could be mapped quantitatively against the neuroanatomic regions of the atlas. Our approach is suitable for studying the effects of gastric dysmotilities on central responses to feeding.