31 results on '"Fogelman I"'
Search Results
2. The effect of nitrogen containing bisphosphonates, zoledronate and alendronate, on the production of pro-angiogenic factors by osteoblastic cells
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Ishtiaq, S., Edwards, S., Sankaralingam, A., Evans, B.A.J., Elford, C., Frost, M.L., Fogelman, I., and Hampson, G.
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- 2015
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3. 18F-NaF PET/CT: EANM procedure guidelines for bone imaging
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Beheshti, M., Mottaghy, F. M., Payche, F., Behrendt, F. F. F., Van den Wyngaert, T., Fogelman, I., Strobel, K., Celli, M., Fanti, S., Giammarile, F., Krause, B., and Langsteger, W.
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- 2015
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4. Treatment of post-menopausal osteoporosis: beyond bisphosphonates
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Ishtiaq, S., Fogelman, I., and Hampson, G.
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- 2015
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5. Changes in bone mineral density and bone turnover in patients on ‘drug holiday’ following bisphosphonate therapy: real-life clinic setting
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Roberts, J., Castro, C., Moore, A. E.B., Fogelman, I., and Hampson, G.
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- 2016
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6. Correction to: 18F-NaF PET/CT: EANM procedure guidelines for bone imaging
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Beheshti, M., Mottaghy, F. M., Paycha, F., Behrendt, F. F. F., Van den Wyngaert, T., Fogelman, I., Strobel, K., Celli, M., Fanti, S., Giammarile, F., Krause, B., and Langsteger, W.
- Published
- 2017
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7. F-18-NaF PET/CT: EANM procedure guidelines for bone imaging (vol 2, pg 1767, 2015)
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Behesti M., Mottaghy F. M., Paycha F., Behrendt F. F. F., Van den Wyngaert T., Fogelman I., Strobel K., Celli M., Fanti S., Giammarile F., Krause B., Langsteger W., and Behesti M., Mottaghy F.M., Paycha F., Behrendt F.F.F., Van den Wyngaert T., Fogelman I., Strobel K., Celli M., Fanti S., Giammarile F., Krause B., Langsteger W.
- Subjects
genetic structures ,Guideline F-18 sodium fluoride PET/CT Bone imaging - Abstract
The aim of this guideline is to provide minimum standards for the performance and interpretation of 18F-NaF PET/CT scans. Standard acquisition and interpretation of nuclear imaging modalities will help to provide consistent data acquisition and numeric values between different platforms and institutes and to promote the use of PET/CT modality as an established diagnostic modality in routine clinical practice. This will also improve the value of scientific work and its contribution to evidence-based medicine.
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- 2018
8. PP.24.09
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Cecelja, M., primary, Edwards, S., additional, Moore, A., additional, Fogelman, I., additional, Chowienczyk, P., additional, and Frost, M., additional
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- 2015
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9. F-NaF PET/CT: EANM procedure guidelines for bone imaging.
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Beheshti, M., Mottaghy, F., Payche, F., Behrendt, F., Wyngaert, T., Fogelman, I., Strobel, K., Celli, M., Fanti, S., Giammarile, F., Krause, B., and Langsteger, W.
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POSITRON emission tomography ,COMPUTED tomography ,DIAGNOSIS of bone diseases ,SODIUM fluoride ,RADIOPHARMACEUTICALS ,NUCLEAR medicine - Abstract
The aim of this guideline is to provide minimum standards for the performance and interpretation of F-NaF PET/CT scans. Standard acquisition and interpretation of nuclear imaging modalities will help to provide consistent data acquisition and numeric values between different platforms and institutes and to promote the use of PET/CT modality as an established diagnostic modality in routine clinical practice. This will also improve the value of scientific work and its contribution to evidence-based medicine. [ABSTRACT FROM AUTHOR]
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- 2015
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10. Correction to: 18F-NaF PET/CT: EANM procedure guidelines for bone imaging.
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Beheshti, M., Mottaghy, F. M., Paycha, F., Behrendt, F. F. F., Van den Wyngaert, T., Fogelman, I., Strobel, K., Celli, M., Fanti, S., Giammarile, F., Krause, B., and Langsteger, W.
- Subjects
DIAGNOSIS of bone diseases ,DIAGNOSTIC imaging ,POSITRON emission tomography - Abstract
The original version of this article unfortunately contained an error. The name and affiliation of 'Frédéric Paycha' needs to be corrected. Given in this article is the correct author name and affiliation. [ABSTRACT FROM AUTHOR]
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- 2018
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11. Clinical validation of the PrecivityAD2 blood test: A mass spectrometry-based test with algorithm combining %p-tau217 and Aβ42/40 ratio to identify presence of brain amyloid.
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Meyer MR, Kirmess KM, Eastwood S, Wente-Roth TL, Irvin F, Holubasch MS, Venkatesh V, Fogelman I, Monane M, Hanna L, Rabinovici GD, Siegel BA, Whitmer RA, Apgar C, Bateman RJ, Holtzman DM, Irizarry M, Verbel D, Sachdev P, Ito S, Contois J, Yarasheski KE, Braunstein JB, Verghese PB, and West T
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- Humans, Female, Male, Aged, Middle Aged, Aged, 80 and over, ROC Curve, Amyloid beta-Peptides blood, tau Proteins blood, Alzheimer Disease blood, Alzheimer Disease diagnosis, Alzheimer Disease diagnostic imaging, Algorithms, Positron-Emission Tomography, Peptide Fragments blood, Brain diagnostic imaging, Brain metabolism, Biomarkers blood, Mass Spectrometry
- Abstract
Background: With the availability of disease-modifying therapies for Alzheimer's disease (AD), it is important for clinicians to have tests to aid in AD diagnosis, especially when the presence of amyloid pathology is a criterion for receiving treatment., Methods: High-throughput, mass spectrometry-based assays were used to measure %p-tau217 and amyloid beta (Aβ)42/40 ratio in blood samples from 583 individuals with suspected AD (53% positron emission tomography [PET] positive by Centiloid > 25). An algorithm (PrecivityAD2 test) was developed using these plasma biomarkers to identify brain amyloidosis by PET., Results: The area under the receiver operating characteristic curve (AUC-ROC) for %p-tau217 (0.94) was statistically significantly higher than that for p-tau217 concentration (0.91). The AUC-ROC for the PrecivityAD2 test output, the Amyloid Probability Score 2, was 0.94, yielding 88% agreement with amyloid PET. Diagnostic performance of the APS2 was similar by ethnicity, sex, age, and apoE4 status., Discussion: The PrecivityAD2 blood test showed strong clinical validity, with excellent agreement with brain amyloidosis by PET., (© 2024 C2N Diagnostics LLC. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
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- 2024
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12. A blood biomarker test for brain amyloid impacts the clinical evaluation of cognitive impairment.
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Monane M, Johnson KG, Snider BJ, Turner RS, Drake JD, Maraganore DM, Bicksel JL, Jacobs DH, Ortega JL, Henderson J, Jiang Y, Huang S, Coppinger J, Fogelman I, West T, and Braunstein JB
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- Humans, Female, Aged, Male, Amyloid beta-Peptides metabolism, Cohort Studies, Prospective Studies, Brain diagnostic imaging, Brain metabolism, Amyloid, Biomarkers, Hematologic Tests, Alzheimer Disease diagnostic imaging, Alzheimer Disease complications, Cognitive Dysfunction diagnosis
- Abstract
Objective: The objective of this study was to examine clinicians' patient selection and result interpretation of a clinically validated mass spectrometry test measuring amyloid beta and ApoE blood biomarkers combined with patient age (PrecivityAD® blood test) in symptomatic patients evaluated for Alzheimer's disease (AD) or other causes of cognitive decline., Methods: The Quality Improvement and Clinical Utility PrecivityAD Clinician Survey (QUIP I, ClinicalTrials.gov Identifier: NCT05477056) was a prospective, single-arm cohort study among 366 patients evaluated by neurologists and other cognitive specialists. Participants underwent blood biomarker testing and received an amyloid probability score (APS), indicating the likelihood of a positive result on an amyloid positron emission tomography (PET) scan. The primary study outcomes were appropriateness of patient selection as well as result interpretation associated with PrecivityAD blood testing., Results: A 95% (347/366) concordance rate was noted between clinicians' patient selection and the test's intended use criteria. In the final analysis including these 347 patients (median age 75 years, 56% women), prespecified test result categories incorporated 133 (38%) low APS, 162 (47%) high APS, and 52 (15%) intermediate APS patients. Clinicians' pretest and posttest AD diagnosis probability changed from 58% to 23% in low APS patients and 71% to 89% in high APS patients (p < 0.0001). Anti-AD drug therapy decreased by 46% in low APS patients (p < 0.0001) and increased by 57% in high APS patients (p < 0.0001)., Interpretation: These findings demonstrate the clinical utility of the PrecivityAD blood test in clinical care and may have added relevance as new AD therapies are introduced., (© 2023 C2N Diagnostics and The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
- Published
- 2023
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13. Independent study demonstrates amyloid probability score accurately indicates amyloid pathology.
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Fogelman I, West T, Braunstein JB, Verghese PB, Kirmess KM, Meyer MR, Contois JH, Shobin E, Ferber KL, Gagnon J, Rubel CE, Graham D, Bateman RJ, Holtzman DM, Huang S, Yu J, Yang S, and Yarasheski KE
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- Humans, Middle Aged, Aged, Plaque, Amyloid diagnostic imaging, Australia, Aging pathology, Amyloid, Amyloid beta-Peptides, Alzheimer Disease diagnostic imaging, Alzheimer Disease pathology
- Abstract
Background: The amyloid probability score (APS) is the model read-out of the analytically validated mass spectrometry-based PrecivityAD
® blood test that incorporates the plasma Aβ42/40 ratio, ApoE proteotype, and age to identify the likelihood of brain amyloid plaques among cognitively impaired individuals being evaluated for Alzheimer's disease., Purpose: This study aimed to provide additional independent evidence that the pre-established APS algorithm, along with its cutoff values, discriminates between amyloid positive and negative individuals., Methods: The diagnostic performance of the PrecivityAD test was analyzed in a cohort of 200 nonrandomly selected Australian Imaging, Biomarker & Lifestyle Flagship Study of Aging (AIBL) study participants, who were either cognitively impaired or healthy controls, and for whom a blood sample and amyloid PET imaging were available., Results: In a subset of the dataset aligned with the Intended Use population (patients aged 60 and older with CDR ≥0.5), the pre-established APS algorithm predicted amyloid PET with a sensitivity of 84.9% (CI: 72.9-92.1%) and specificity of 96% (CI: 80.5-99.3%), exclusive of 13 individuals for whom the test was inconclusive., Interpretation: The study shows individuals with a high APS are more likely than those with a low APS to have abnormal amounts of amyloid plaques and be on an amyloid accumulation trajectory, a dynamic and evolving process characteristic of progressive AD pathology. Exploratory data suggest APS retains its diagnostic performance in healthy individuals, supporting further screening studies in the cognitively unimpaired., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)- Published
- 2023
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14. Assessment of a Plasma Amyloid Probability Score to Estimate Amyloid Positron Emission Tomography Findings Among Adults With Cognitive Impairment.
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Hu Y, Kirmess KM, Meyer MR, Rabinovici GD, Gatsonis C, Siegel BA, Whitmer RA, Apgar C, Hanna L, Kanekiyo M, Kaplow J, Koyama A, Verbel D, Holubasch MS, Knapik SS, Connor J, Contois JH, Jackson EN, Harpstrite SE, Bateman RJ, Holtzman DM, Verghese PB, Fogelman I, Braunstein JB, Yarasheski KE, and West T
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- Aged, Amyloid, Amyloid beta-Peptides analysis, Apolipoproteins E genetics, Cohort Studies, Cross-Sectional Studies, Female, Humans, Male, Peptide Fragments, Plaque, Amyloid diagnostic imaging, Positron-Emission Tomography, Probability, Prospective Studies, Alzheimer Disease diagnostic imaging, Amyloidosis, Cognitive Dysfunction diagnostic imaging
- Abstract
Importance: The diagnostic evaluation for Alzheimer disease may be improved by a blood-based diagnostic test identifying presence of brain amyloid plaque pathology., Objective: To determine the clinical performance associated with a diagnostic algorithm incorporating plasma amyloid-β (Aβ) 42:40 ratio, patient age, and apoE proteotype to identify brain amyloid status., Design, Setting, and Participants: This cohort study includes analysis from 2 independent cross-sectional cohort studies: the discovery cohort of the Plasma Test for Amyloidosis Risk Screening (PARIS) study, a prospective add-on to the Imaging Dementia-Evidence for Amyloid Scanning study, including 249 patients from 2018 to 2019, and MissionAD, a dataset of 437 biobanked patient samples obtained at screenings during 2016 to 2019. Data were analyzed from May to November 2020., Exposures: Amyloid detected in blood and by positron emission tomography (PET) imaging., Main Outcomes and Measures: The main outcome was the diagnostic performance of plasma Aβ42:40 ratio, together with apoE proteotype and age, for identifying amyloid PET status, assessed by accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC)., Results: All 686 participants (mean [SD] age 73.2 [6.3] years; 368 [53.6%] men; 378 participants [55.1%] with amyloid PET findings) had symptoms of mild cognitive impairment or mild dementia. The AUC of plasma Aβ42:40 ratio for PARIS was 0.79 (95% CI, 0.73-0.85) and 0.86 (95% CI, 0.82-0.89) for MissionAD. Ratio cutoffs for Aβ42:40 based on the Youden index were similar between cohorts (PARIS: 0.089; MissionAD: 0.092). A logistic regression model (LRM) incorporating Aβ42:40 ratio, apoE proteotype, and age improved diagnostic performance within each cohort (PARIS: AUC, 0.86 [95% CI, 0.81-0.91]; MissionAD: AUC, 0.89 [95% CI, 0.86-0.92]), and overall accuracy was 78% (95% CI, 72%-83%) for PARIS and 83% (95% CI, 79%-86%) for MissionAD. The model developed on the prospectively collected samples from PARIS performed well on the MissionAD samples (AUC, 0.88 [95% CI, 0.84-0.91]; accuracy, 78% [95% CI, 74%-82%]). Training the LRM on combined cohorts yielded an AUC of 0.88 (95% CI, 0.85-0.91) and accuracy of 81% (95% CI, 78%-84%). The output of this LRM is the Amyloid Probability Score (APS). For clinical use, 2 APS cutoff values were established yielding 3 categories, with low, intermediate, and high likelihood of brain amyloid plaque pathology., Conclusions and Relevance: These findings suggest that this blood biomarker test could allow for distinguishing individuals with brain amyloid-positive PET findings from individuals with amyloid-negative PET findings and serve as an aid for Alzheimer disease diagnosis.
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- 2022
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15. The PrecivityAD™ test: Accurate and reliable LC-MS/MS assays for quantifying plasma amyloid beta 40 and 42 and apolipoprotein E proteotype for the assessment of brain amyloidosis.
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Kirmess KM, Meyer MR, Holubasch MS, Knapik SS, Hu Y, Jackson EN, Harpstrite SE, Verghese PB, West T, Fogelman I, Braunstein JB, Yarasheski KE, and Contois JH
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- Amyloid beta-Peptides metabolism, Apolipoprotein E4, Apolipoproteins E genetics, Biomarkers, Brain metabolism, Chromatography, Liquid, Humans, Peptide Fragments, Tandem Mass Spectrometry, Alzheimer Disease, Amyloidosis diagnosis, Amyloidosis genetics
- Abstract
Background: There is an unmet need for an accessible, less invasive, cost-effective method to facilitate clinical trial enrollment and aid in clinical Alzheimer's disease (AD) diagnosis. APOE genotype affects the clearance and deposition of amyloid-beta (Aβ) with APOE4 carriers having increased risk while APOE2 alleles appear to be protective. Lower plasma Aβ42/40 correlates with brain amyloidosis. In response, C
2 N has developed the PrecivityAD™ test; plasma LC-MS/MS assays for Aβ isoform quantitation and qualitative APOE isoform-specific proteotyping., Methods: In accord with CLIA standards, we developed and validated assay performance: precision, accuracy, linearity, limit of detection (LoD), interferences., Results: Within-day precision varied from 1.5-3.0% (Aβ40) and 2.5-8.4% (Aβ42). Total (within-lab) variability was 2.7-7.7% (Aβ40) and 3.1-9.5% (Aβ42). Aβ40 quantitation was linear from 10 to 1780 pg/mL; Aβ42 was linear from 2 to 254 pg/mL. LoD was 11 and 2 pg/mL for Aβ40 and Aβ42, respectively. APOE proteotypes were 100% concordant with genotype, while LoD (fM) was much lower than APOE concentrations observed in plasma (mM)., Conclusions: The PrecivityAD™ assays are precise, accurate, sensitive, and linear over a wide analytical range, free from significant interferences, and suitable for use in the clinical laboratory., (Copyright © 2021 C2N Diagnostics. Published by Elsevier B.V. All rights reserved.)- Published
- 2021
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16. Comparison of ordered-subset expectation maximization and filtered back projection reconstruction based on quantitative outcome from dynamic [18F]NaF PET images.
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Wong JM, Puri T, Siddique MM, Frost ML, Moore AEB, Blake GM, and Fogelman I
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- Humans, Female, Middle Aged, Aged, Algorithms, Artifacts, Positron-Emission Tomography methods, Image Processing, Computer-Assisted methods, Sodium Fluoride, Fluorine Radioisotopes
- Abstract
[18F]NaF PET imaging is a useful tool for measuring regional bone metabolism. However, due to tracer in urine, [18F]NaF PET images of the hip reconstructed using filtered back projection (FBP) frequently show streaking artifacts in slices through the bladder leading to noisy time-activity curves unsuitable for quantification. This study compares differences between quantitative outcomes at the hip derived from images reconstructed using the FBP and ordered-subset expectation maximization (OSEM) methods. Dynamic [18F]NaF PET data at the hip for four postmenopausal women were reconstructed using FBP and nine variations of the OSEM algorithm (all combinations of 1, 5, 15 iterations and 10, 15, 21 subsets). Seven volumes of interest were placed in the hip. Bone metabolism was measured using standardized uptake values, Patlak analysis (Ki-PAT) and Hawkins model Ki-4k. Percentage differences between the standardized uptake values and Ki values from FBP and OSEM images were assessed. OSEM images appeared visually smoother and without the streaking artifacts seen with FBP. However, due to loss of counts, they failed to recover the quantitative values in VOIs close to the bladder, including the femoral head and femoral neck. This was consistent for all quantification methods. Volumes of interest farther from the bladder or larger and receiving greater counts showed good convergence with 5 iterations and 21 subsets. For VOIs close to the bladder, including the femoral neck and femoral head, 15 iterations and 10, 15 or 21 subsets were not enough to obtain OSEM images suitable for measuring bone metabolism and showed no improvement compared to FBP., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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17. A blood-based diagnostic test incorporating plasma Aβ42/40 ratio, ApoE proteotype, and age accurately identifies brain amyloid status: findings from a multi cohort validity analysis.
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West T, Kirmess KM, Meyer MR, Holubasch MS, Knapik SS, Hu Y, Contois JH, Jackson EN, Harpstrite SE, Bateman RJ, Holtzman DM, Verghese PB, Fogelman I, Braunstein JB, and Yarasheski KE
- Subjects
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease blood, Alzheimer Disease cerebrospinal fluid, Alzheimer Disease diagnostic imaging, Amyloid analysis, Amyloid beta-Peptides cerebrospinal fluid, Apolipoprotein E4 blood, Apolipoprotein E4 genetics, Area Under Curve, Biomarkers, Blood Specimen Collection methods, Brain diagnostic imaging, Brain Chemistry, Chromatography, Liquid, Cohort Studies, Female, Gene Dosage, Humans, Middle Aged, Peptide Fragments cerebrospinal fluid, Positron-Emission Tomography, Predictive Value of Tests, ROC Curve, Tandem Mass Spectrometry, Alzheimer Disease diagnosis, Amyloid beta-Peptides blood, Apolipoproteins E blood, Peptide Fragments blood
- Abstract
Background: The development of blood-based biomarker tests that are accurate and robust for Alzheimer's disease (AD) pathology have the potential to aid clinical diagnosis and facilitate enrollment in AD drug trials. We developed a high-resolution mass spectrometry (MS)-based test that quantifies plasma Aβ42 and Aβ40 concentrations and identifies the ApoE proteotype. We evaluated robustness, clinical performance, and commercial viability of this MS biomarker assay for distinguishing brain amyloid status., Methods: We used the novel MS assay to analyze 414 plasma samples that were collected, processed, and stored using site-specific protocols, from six independent US cohorts. We used receiver operating characteristic curve (ROC) analyses to assess assay performance and accuracy for predicting amyloid status (positive, negative, and standard uptake value ratio; SUVR). After plasma analysis, sites shared brain amyloid status, defined using diverse, site-specific methods and cutoff values; amyloid PET imaging using various tracers or CSF Aβ42/40 ratio., Results: Plasma Aβ42/40 ratio was significantly (p < 0.001) lower in the amyloid positive vs. negative participants in each cohort. The area under the ROC curve (AUC-ROC) was 0.81 (95% CI = 0.77-0.85) and the percent agreement between plasma Aβ42/40 and amyloid positivity was 75% at the optimal (Youden index) cutoff value. The AUC-ROC (0.86; 95% CI = 0.82-0.90) and accuracy (81%) for the plasma Aβ42/40 ratio improved after controlling for cohort heterogeneity. The AUC-ROC (0.90; 95% CI = 0.87-0.93) and accuracy (86%) improved further when Aβ42/40, ApoE4 copy number and participant age were included in the model., Conclusions: This mass spectrometry-based plasma biomarker test: has strong diagnostic performance; can accurately distinguish brain amyloid positive from amyloid negative individuals; may aid in the diagnostic evaluation process for Alzheimer's disease; and may enhance the efficiency of enrolling participants into Alzheimer's disease drug trials.
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- 2021
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18. Evaluation of aortic 18 F-NaF tracer uptake using PET/CT as a predictor of aortic calcification in postmenopausal women: A longitudinal study.
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Cecelja M, Moore A, Fogelman I, Frost ML, Blake GM, and Chowienczyk P
- Abstract
Introduction: Aortic calcification as detected by computed tomography is associated with arterial stiffening and is an important predictor of cardiovascular morbidity and mortality. Uptake of
18 F-sodium fluoride (18 F-NaF) in the aortic wall reflects metabolically active areas of calcification. The aim of this study was to determine if18 F-NaF uptake in the aorta is associated with calcification and progression of calcification as detected by computed tomography., Methods: Twenty-one postmenopausal women (mean age 62 ± 6 years) underwent assessment of aortic18 F-NaF uptake using positron emission tomography/computer tomography at baseline and a repeat computed tomography scan after a mean follow-up of 3.8 ± 1.3 years. Tracer uptake was quantified by calculating the target-to-background (TBR) ratios at baseline and follow-up. Calcification was assessed at baseline and follow-up using computed tomography., Results: Over the follow-up period, aortic calcium volume increased from 0.46 ± 0.62 to 0.71 ± 0.93 cm3 ( P < 0.05). However, the change in calcium volume did not correlate with baseline TBR either unadjusted ( r = 0.00, P = 1.00) or adjusted for age and baseline calcium volume (beta coefficient = -0.18, P = 0.42). TBR at baseline did not differ between participants with ( n = 16) compared to those without ( n = 5) progression in calcium volume (2.43 ± 0.46 vs. 2.31 ± 0.38, P = 0.58). In aortic segments identified to have the highest tracer uptake at baseline, calcium volume did not significantly change over the follow-up period ( P = 0.41)., Conclusion: In a cohort of postmenopausal women,18 F-NaF uptake as measured by TBR in the lumbar aorta did not predict progression of aortic calcification as detected by computed tomography over a four-year follow-up.- Published
- 2019
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19. Site specific measurements of bone formation using [ 18 F] sodium fluoride PET/CT.
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Blake GM, Puri T, Siddique M, Frost ML, Moore AEB, and Fogelman I
- Abstract
Dynamic positron emission tomography (PET) imaging with fluorine-18 labelled sodium fluoride ([
18 F]NaF) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. Today, hybrid PET and computed tomography (CT) dual-modality systems (PET/CT) are widely available, and [18 F]NaF PET/CT offers a convenient non-invasive method of studying bone formation at the important osteoporotic fracture sites at the hip and spine, as well as sites of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers or bone biopsy as a tool to investigate new therapies for osteoporosis, and has a potential role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing dynamic [18 F]NaF PET/CT scan data, and outlines a simplified approach combining venous blood sampling with a series of short (3- to 5-minute) static PET/CT scans acquired at different bed positions to estimate [18 F]NaF plasma clearance at multiple sites in the skeleton with just a single injection of tracer., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.- Published
- 2018
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20. Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy.
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Yanamandra K, Patel TK, Jiang H, Schindler S, Ulrich JD, Boxer AL, Miller BL, Kerwin DR, Gallardo G, Stewart F, Finn MB, Cairns NJ, Verghese PB, Fogelman I, West T, Braunstein J, Robinson G, Keyser J, Roh J, Knapik SS, Hu Y, and Holtzman DM
- Subjects
- Animals, Brain metabolism, Disease Models, Animal, Dose-Response Relationship, Drug, Humans, Mice, Mice, Transgenic, Nitro Compounds toxicity, Propionates toxicity, Antibodies pharmacology, Tauopathies blood, Tauopathies metabolism, tau Proteins blood, tau Proteins metabolism
- Abstract
Tauopathies are a group of disorders in which the cytosolic protein tau aggregates and accumulates in cells within the brain, resulting in neurodegeneration. A promising treatment being explored for tauopathies is passive immunization with anti-tau antibodies. We previously found that administration of an anti-tau antibody to human tau transgenic mice increased the concentration of plasma tau. We further explored the effects of administering an anti-tau antibody on plasma tau. After peripheral administration of an anti-tau antibody to human patients with tauopathy and to mice expressing human tau in the central nervous system, there was a dose-dependent increase in plasma tau. In mouse plasma, we found that tau had a short half-life of 8 min that increased to more than 3 hours after administration of anti-tau antibody. As tau transgenic mice accumulated insoluble tau in the brain, brain soluble and interstitial fluid tau decreased. Administration of anti-tau antibody to tau transgenic mice that had decreased brain soluble tau and interstitial fluid tau resulted in an increase in plasma tau, but this increase was less than that observed in tau transgenic mice without these brain changes. Tau transgenic mice subjected to acute neuronal injury using 3-nitropropionic acid showed increased interstitial fluid tau and plasma tau. These data suggest that peripheral administration of an anti-tau antibody results in increased plasma tau, which correlates with the concentration of extracellular and soluble tau in the brain., (Copyright © 2017, American Association for the Advancement of Science.)
- Published
- 2017
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21. Preclinical and Clinical Development of ABBV-8E12, a Humanized Anti-Tau Antibody, for Treatment of Alzheimer's Disease and Other Tauopathies.
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West T, Hu Y, Verghese PB, Bateman RJ, Braunstein JB, Fogelman I, Budur K, Florian H, Mendonca N, and Holtzman DM
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- Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized pharmacokinetics, Double-Blind Method, Drug Evaluation, Preclinical, Humans, Immunologic Factors adverse effects, Immunologic Factors pharmacokinetics, Immunotherapy, Models, Biological, Tauopathies blood, Tauopathies cerebrospinal fluid, Antibodies, Monoclonal, Humanized therapeutic use, Immunologic Factors therapeutic use, Tauopathies therapy
- Abstract
Tau neurofibrillary tangles are found in the brains of patients suffering from Alzheimer's disease and other tauopathies. The progressive spreading of tau pathology from one brain region to the next is believed to be caused by extracellular transsynaptic transmission of misfolded tau between neurons. Preclinical studies have shown that antibodies against tau can prevent this transfer of misfolded tau between cells. Thus, antibodies against tau have the potential to stop or slow the progression of tau pathology observed in human tauopathies. To test this hypothesis, a humanized anti-tau antibody (ABBV-8E12) was developed and a phase 1 clinical trial of this antibody has been completed. The double-blind, placebo-controlled phase 1 study tested single doses of ABBV-8E12 ranging from 2.5 to 50 mg/kg in 30 patients with progressive supranuclear palsy (PSP). ABBV-8E12 was found to have an acceptable safety profile with no clinically concerning trends in the number or severity of adverse events between the placebo and dosed groups. Pharmacokinetic modelling showed that the antibody has a plasma half-life and cerebrospinal fluid:plasma ratio consistent with other humanized antibodies, and there were no signs of immunogenicity against ABBV-8E12. Based on the acceptable safety and tolerability profile of single doses of ABBV-8E12, AbbVie is currently enrolling patients into two phase 2 clinical trials to assess efficacy and safety of multiple doses of ABBV-8E12 in patients with early Alzheimer's disease or PSP., Competing Interests: TW, IHH, PBV, and IF are full time employees and/or advisors of C2N Diagnostics, receiving stock and/or stock options. RJB is a co-founder of C2N Diagnostics. RJB and Washington University in St. Louis have equity ownership interest in C2N Diagnostics and may receive royalty income based on technology licensed by Washington University to C2N Diagnostics. RJB receives lab research funding from the Tau SILK Consortium (AbbVie, Biogen, and Eli Lilly and Co.), Eli Lilly and Co, Hoffman La-Roche, Janssen, Avid Radiopharmaceuticals, and the DIAN Pharma Consortium (Abbvie, Amgen, AstraZeneca, Biogen, Eisai, Eli Lilly and Co, Hoffman La-Roche, Janssen, Pfizer, and Sanofi). RJB has received honoraria from Janssen and Pfizer as a speaker and from Merck and Pfizer as an Advisory Board member. In addition, RJB receives income from C2N Diagnostics for serving on the Scientific Advisory Board. JBB is a co-founder and employee of C2N Diagnostics, receiving stock and/or stock options. KB, HF, and NM are employees of AbbVie, receiving stock and/or stock options. DMH co-founded and is on the scientific advisory board of C2N Diagnostics. DMH is an inventor on a submitted patent “Antibodies to Tau”, PCT/US2013/049333, that is licensed by Washington University to C2N Diagnostics. This patent was subsequently licensed to AbbVie. DMH receives research grants from the C2N Diagnostics, AbbVie, Eli Lilly, and Denali. DMH consults for Genentech, AbbVie, Eli Lilly, Proclara Biosciences, Glaxosmithkline, and Denali.
- Published
- 2017
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22. Prospective comparison of whole-body bone SPECT and sodium 18F-fluoride PET in the detection of bone metastases from breast cancer.
- Author
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Abikhzer G, Srour S, Fried G, Drumea K, Kozlener E, Frenkel A, Israel O, Fogelman I, and Kagna O
- Subjects
- Adult, Aged, Female, Fluorine Radioisotopes, Humans, Middle Aged, Positron Emission Tomography Computed Tomography methods, Prospective Studies, Radiopharmaceuticals, Sodium Fluoride, Technetium Tc 99m Medronate, Bone Neoplasms diagnostic imaging, Bone Neoplasms secondary, Breast Neoplasms diagnostic imaging, Positron-Emission Tomography methods, Tomography, Emission-Computed, Single-Photon methods
- Abstract
Objective: The superiority of sodium F-fluoride PET (F-PET)/computed tomography (CT) over planar and single field-of-view single-photon emission computed tomography (SPECT) bone scintigraphy with Tc-methylene diphosphonate in bone metastases detection has been established. The present study prospectively compares whole-body Tc-methylene diphosphonate SPECT (WB-SPECT) and F-PET performance indices for the detection of bone metastases in breast cancer., Methods: A total of 41 pairs of studies in female breast cancer patients (average age 58 years, range 30-75) were included. Half-time WB-SPECT and F-PET/CT were performed at a 4-day average interval (range 0-36 days), with subsequent fusion of CT to WB-SPECT. Two readers independently interpreted the studies, with differences resolved by consensus. Composite gold standard included the CT component of the F-PET/CT study with follow-up CT, MRI, F-fluoro-deoxyglucose-PET/CT, and bone scans., Results: On patient-based analysis, metastases were diagnosed in 21 patients, with 19 patients detected by WB-SPECT and 21 with F-PET, the latter being the only modality to detect a single metastasis in two patients. The sensitivity of WB-SPECT and F-PET was 90 and 100% (P=NS), and the specificity were 95 and 85%, respectively (P=NS). On lesion-based analysis, 284 total sites of increased uptake were found. WB-SPECT detected 171/284 (60%) and F-PET 268/284 (94%) lesions, with good interobserver agreement for WB-SPECT (κ=0.679) and excellent agreement for F-PET (κ=0.798). The final analysis classified 204 lesions as benign and 80 as metastases. WB-SPECT identified 121 benign and 50 malignant sites compared with 192 and 76, respectively, for F-PET. WB-SPECT and F-PET had a sensitivity of 63 vs. 95%, P-value of less than 0.001, and a specificity of 97 vs. 96% (P=NS), respectively, on lesion-based analysis., Conclusion: F-PET had higher sensitivity for the diagnosis of bone metastases from breast cancer compared with WB-SPECT, showing a statistically significant 32% increase on lesion-based analysis.
- Published
- 2016
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23. Hormone Replacement Therapy Versus the Combined Oral Contraceptive Pill in Premature Ovarian Failure: A Randomized Controlled Trial of the Effects on Bone Mineral Density.
- Author
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Cartwright B, Robinson J, Seed PT, Fogelman I, and Rymer J
- Subjects
- Adolescent, Adult, Case-Control Studies, Female, Follow-Up Studies, Humans, Prognosis, Young Adult, Bone Density drug effects, Contraceptives, Oral, Combined therapeutic use, Hormone Replacement Therapy, Primary Ovarian Insufficiency drug therapy
- Abstract
Context: Women with premature ovarian failure (POF) face many years of estrogen deficiency. One of the major consequences is bone loss. The optimal form of estrogen replacement is unknown and management is not evidence based. The 2 broad options are combined hormone replacement therapy (HRT) or the combined oral contraceptive pill (COCP)., Objectives: To compare the effects of HRT and COCP on bone density and turnover in women with spontaneous POF and to observe the effects of no treatment., Design: Two-year open randomized trial comparing HRT and COCP and nonrandomized observation of women declining treatment using the same protocol., Setting: London teaching hospital., Participants: A total of 59 women with spontaneous POF aged 18-44, 30 women elected to take treatment and were randomized, and 29 declined treatment., Intervention: Randomization was to HRT (Nuvelle) or COCP (Microgynon 30)., Main Outcome Measures: The primary outcome was change in lumbar spine bone mineral density. Changes in total hip and femoral neck bone density and bone turnover markers were also assessed., Results: A total of 36 women (61%) completed the trial (no treatment 52%; HRT 60%; COCP 80%). In comparison with COCP, treatment with HRT increased bone density at the lumbar spine at 2 years (+0.050 g/cm(2); 95% confidence interval 0.007-0.092; P = .025). Bone turnover markers showed similar reductions in the 2 treatment groups. In the no treatment group, bone density dropped at all sites and bone turnover markers remained relatively unchanged., Conclusions: The results suggest that HRT is superior to COCP in increasing bone density at the lumbar spine in women with spontaneous POF. The limitations of a small sample size and high drop-out rate mean that further research is required to confirm the findings. However, either treatment is clearly superior to no treatment.
- Published
- 2016
- Full Text
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24. Interesting Signs in Nuclear Medicine.
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Gnanasegaran G, Sit C, Chen R, Agrawal K, and Fogelman I
- Subjects
- Humans, Positron-Emission Tomography, Radiopharmaceuticals, Tomography, Emission-Computed, Single-Photon, Nuclear Medicine, Radionuclide Imaging
- Abstract
Classic radiological and nuclear medicine signs have been reported extensively because of a myriad of pathophysiological processes. When encountered, they aid in diagnosis of conditions and add confidence for the reader, at times even hinting at a specific diagnosis. The naming of signs is commonly associated with objects from everyday life to establish familiarity with visual findings. Association of signs and disease comes with regular practice and improves understanding of the image and its underlying cause. In this article, we have collated nuclear medicine signs reported in the literature since 1970., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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25. Pitfalls and Limitations of Radionuclide and Hybrid Imaging: Part 2.
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Gnanasegaran G and Fogelman I
- Subjects
- Humans, Magnetic Resonance Imaging, Positron-Emission Tomography, Tomography, Emission-Computed, Single-Photon, Tomography, X-Ray Computed, Multimodal Imaging methods, Radionuclide Imaging methods
- Published
- 2015
- Full Text
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26. Pitfalls and Limitations of Radionuclide Planar and Hybrid Bone Imaging.
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Agrawal K, Marafi F, Gnanasegaran G, Van der Wall H, and Fogelman I
- Subjects
- Animals, Artifacts, Bone Neoplasms diagnostic imaging, Diagnosis, Differential, Humans, Bone and Bones diagnostic imaging, Multimodal Imaging methods, Radionuclide Imaging methods
- Abstract
The radionuclide (99m)Tc-MDP bone scan is one of the most commonly performed nuclear medicine studies and helps in the diagnosis of different pathologies relating to the musculoskeletal system. With its increasing utility in clinical practice, it becomes more important to be aware of various limitations of this imaging modality to avoid false interpretation. It is necessary to be able to recognize various technical, radiopharmaceutical, and patient-related artifacts that can occur while carrying out a bone scan. Furthermore, several normal variations of tracer uptake may mimic pathology and should be interpreted cautiously. There is an important limitation of a bone scan in metastatic disease evaluation as the inherent mechanism of tracer uptake is not specific for tumor but primarily relies on an osteoblastic response. Thus, it is crucial to keep in mind uptake in benign lesions, which can resemble malignant pathologies. The utility of a planar bone scan in benign orthopedic diseases, especially at sites with complex anatomy, is limited owing to lack of precise anatomical information. SPECT/CT has been significantly helpful in these cases. With wider use of PET/CT and reintroduction of the (18)F-fluoride bone scan, increasing knowledge of potential pitfalls on an (18)F-fluoride bone scan and (18)F-FDG-PET/CT will help in improving the accuracy of clinical reports., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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27. Pitfalls and Limitations of Radionuclide Imaging in Endocrinology.
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Agrawal K, Esmail AA, Gnanasegaran G, Navalkissoor S, Mittal BR, and Fogelman I
- Subjects
- Humans, Neuroendocrine Tumors diagnostic imaging, Parathyroid Glands diagnostic imaging, Thyroid Diseases diagnostic imaging, Endocrinology methods, Radionuclide Imaging methods
- Abstract
Several different techniques, radiopharmaceuticals, and imaging modalities are commonly used in nuclear medicine for studies of endocrine organs. Nuclear medicine is used in the management of benign and malignant thyroid, parathyroid, and neuroendocrine disorders. Thus, it is essential to acknowledge pitfalls and the limitations of nuclear medicine imaging for accurate diagnosis and patient management., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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28. Letter from the Guest Editor: Pitfalls and Limitations of Radionuclide and Hybrid Imaging--Part I.
- Author
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Gnanasegaran G and Fogelman I
- Subjects
- Adult, Child, Humans, Multimodal Imaging, Radionuclide Imaging
- Published
- 2015
- Full Text
- View/download PDF
29. Obesity increases precision errors in total body dual-energy x-ray absorptiometry measurements.
- Author
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Knapp KM, Welsman JR, Hopkins SJ, Shallcross A, Fogelman I, and Blake GM
- Subjects
- Adolescent, Adult, Aged, Body Mass Index, Case-Control Studies, Female, Humans, Middle Aged, Overweight diagnostic imaging, Reproducibility of Results, Young Adult, Absorptiometry, Photon, Adipose Tissue diagnostic imaging, Bone Density, Bone and Bones diagnostic imaging, Obesity diagnostic imaging
- Abstract
Total body (TB) dual-energy X-ray absorptiometry (DXA) is increasingly being used to measure body composition in research and clinical settings. This study investigated the effect of body mass index (BMI) and body fat on precision errors for total and regional TB DXA measurements of bone mineral density, fat tissue, and lean tissue using the GE Lunar Prodigy (GE Healthcare, Bedford, UK). One hundred forty-four women with BMI's ranging from 18.5 to 45.9 kg/m(2) were recruited. Participants had duplicate DXA scans of the TB with repositioning between examinations. Participants were divided into 3 groups based on their BMI, and the root mean square standard deviation and the percentage coefficient of variation were calculated for each group. The root mean square standard deviation (percentage coefficient of variation) for the normal (<25 kg/m²; n = 76), overweight (25-30 kg/m²; n = 36), and obese (>30 kg/m²; n = 32) BMI groups, respectively, were total BMD (g/cm(2)): 0.009 (0.77%), 0.009 (0.69%), 0.011 (0.91%); total fat (g): 545 (2.98%), 486 (1.72%), 677 (1.55%); total lean (g): 551 (1.42%), 540 (1.34%), and 781 (1.68%). These results suggest that serial measurements in obese subjects should be treated with caution because the least significant change may be larger than anticipated., (Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
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30. Osteopetrosis: radiological & radionuclide imaging.
- Author
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Sit C, Agrawal K, Fogelman I, and Gnanasegaran G
- Abstract
Osteopetrosis is a rare inherited bone disease where bones harden and become abnormally dense. While the diagnosis is clinical, it also greatly relies on appearance of the skeleton radiographically. X-ray, radionuclide bone scintigraphy and magnetic resonance imaging have been reported to identify characteristics of osteopetrosis. We present an interesting case of a 59-year-old man with a history of bilateral hip fractures. He underwent (99m)Tc-methylene diphosphonate whole body scan supplemented with single-photon emission computed tomography/computed tomography of spine, which showed increased uptake in the humeri, tibiae and femora, which were in keeping with osteopetrosis.
- Published
- 2015
- Full Text
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31. Imaging of site specific bone turnover in osteoporosis using positron emission tomography.
- Author
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Blake GM, Siddique M, Frost ML, Moore AE, and Fogelman I
- Subjects
- Diagnostic Imaging, Fluorine Radioisotopes, Humans, Mathematical Computing, Osteogenesis, Time Factors, Bone and Bones metabolism, Osteoporosis diagnostic imaging, Osteoporosis metabolism, Positron-Emission Tomography methods
- Abstract
The functional imaging technique of dynamic fluorine-18 labeled sodium fluoride positron emission tomography ((18)F-NaF PET) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. (18)F-NaF PET provides a novel and noninvasive method of studying site-specific bone formation at the hip and spine, as well as areas of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers and bone biopsy as a tool to investigate new treatments for osteoporosis, and holds promise of a future role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing (18)F-NaF PET scan data, and outlines a simplified approach that uses 5-minute static PET scan images combined with venous blood samples to estimate (18)F-NaF plasma clearance at multiple sites in the skeleton with a single injection of tracer.
- Published
- 2014
- Full Text
- View/download PDF
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