Browsing by Subject "Positron-Emission Tomography"
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Item Open Access Brain connectivity and visual attention.(Brain connectivity, 2013-01) Parks, Emily L; Madden, David JEmerging hypotheses suggest that efficient cognitive functioning requires the integration of separate, but interconnected cortical networks in the brain. Although task-related measures of brain activity suggest that a frontoparietal network is associated with the control of attention, little is known regarding how components within this distributed network act together or with other networks to achieve various attentional functions. This review considers both functional and structural studies of brain connectivity, as complemented by behavioral and task-related neuroimaging data. These studies show converging results: The frontal and parietal cortical regions are active together, over time, and identifiable frontoparietal networks are active in relation to specific task demands. However, the spontaneous, low-frequency fluctuations of brain activity that occur in the resting state, without specific task demands, also exhibit patterns of connectivity that closely resemble the task-related, frontoparietal attention networks. Both task-related and resting-state networks exhibit consistent relations to behavioral measures of attention. Further, anatomical structure, particularly white matter pathways as defined by diffusion tensor imaging, places constraints on intrinsic functional connectivity. Lastly, connectivity analyses applied to investigate cognitive differences across individuals in both healthy and diseased states suggest that disconnection of attentional networks is linked to deficits in cognitive functioning, and in extreme cases, to disorders of attention. Thus, comprehensive theories of visual attention and their clinical translation depend on the continued integration of behavioral, task-related neuroimaging, and brain connectivity measures.Item Open Access Complete Evaluation of Dementia: PET and MRI Correlation and Diagnosis for the Neuroradiologist.(AJNR. American journal of neuroradiology, 2021-06) Oldan, JD; Jewells, VL; Pieper, B; Wong, TZThis article will familiarize neuroradiologists with the pathophysiology, clinical findings, and standard MR imaging and PET imaging features of multiple forms of dementia as well as new emerging techniques. Cases were compiled from multiple institutions with the goal of improved diagnostic accuracy and improved patient care as well as information about biomarkers on the horizon. Dementia topics addressed include the following: Alzheimer disease, frontotemporal dementia, cerebral amyloid angiopathy, Lewy body dementia, Parkinson disease and Parkinson disease variants, amyotrophic lateral sclerosis, multisystem atrophy, Huntington disease vascular dementia, and Creutzfeldt-Jakob disease.Item Open Access Evaluating Alzheimer Disease With Flortaucipir and Florbetapir PET: A Clinical Case Series.(Clinical nuclear medicine, 2021-07) James, Olga G; Linares, Alexandra R; Hellegers, Caroline; Doraiswamy, P Murali; Wong, Terence ZAbstract
Early, accurate diagnosis of Alzheimer disease (AD) is essential but remains challenging. Neuropathological hallmarks of AD are β-amyloid neuritic plaques and tau protein neurofibrillary tangles. 18F-Florbetapir is one of several available PET tracers for imaging cortical fibrillary β-amyloid plaques. 18F-Flortaucipir PET was recently approved for evaluating the distribution and density of aggregated neurofibrillary tangles. We present cases of mild cognitive impairment or suspected AD to depict the nuances of flortaucipir distribution and scan interpretation as well as how combined information from amyloid and tau PET may help with differential diagnosis and prognosis.Item Open Access Imaging biomarker roadmap for cancer studies.(Nature reviews. Clinical oncology, 2017-03) O'Connor, James PB; Aboagye, Eric O; Adams, Judith E; Aerts, Hugo JWL; Barrington, Sally F; Beer, Ambros J; Boellaard, Ronald; Bohndiek, Sarah E; Brady, Michael; Brown, Gina; Buckley, David L; Chenevert, Thomas L; Clarke, Laurence P; Collette, Sandra; Cook, Gary J; deSouza, Nandita M; Dickson, John C; Dive, Caroline; Evelhoch, Jeffrey L; Faivre-Finn, Corinne; Gallagher, Ferdia A; Gilbert, Fiona J; Gillies, Robert J; Goh, Vicky; Griffiths, John R; Groves, Ashley M; Halligan, Steve; Harris, Adrian L; Hawkes, David J; Hoekstra, Otto S; Huang, Erich P; Hutton, Brian F; Jackson, Edward F; Jayson, Gordon C; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O; Lee, Ting-Yim; Leen, Edward L; Lewis, Jason S; Liu, Yan; Lythgoe, Mark F; Manoharan, Prakash; Maxwell, Ross J; Miles, Kenneth A; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R; Parker, Geoff JM; Partridge, Mike; Pathak, Arvind P; Peet, Andrew C; Punwani, Shonit; Reynolds, Andrew R; Robinson, Simon P; Shankar, Lalitha K; Sharma, Ricky A; Soloviev, Dmitry; Stroobants, Sigrid; Sullivan, Daniel C; Taylor, Stuart A; Tofts, Paul S; Tozer, Gillian M; van Herk, Marcel; Walker-Samuel, Simon; Wason, James; Williams, Kaye J; Workman, Paul; Yankeelov, Thomas E; Brindle, Kevin M; McShane, Lisa M; Jackson, Alan; Waterton, John CImaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Item Open Access Imaging of musculoskeletal bacterial infections by [124I]FIAU-PET/CT.(PLoS One, 2007-10-10) Diaz, Luis A; Foss, Catherine A; Thornton, Katherine; Nimmagadda, Sridhar; Endres, Christopher J; Uzuner, Ovsev; Seyler, Thorsten M; Ulrich, Slif D; Conway, Janet; Bettegowda, Chetan; Agrawal, Nishant; Cheong, Ian; Zhang, Xiaosong; Ladenson, Paul W; Vogelstein, Barry N; Mont, Michael A; Zhou, Shibin; Kinzler, Kenneth W; Vogelstein, Bert; Pomper, Martin GBACKGROUND: Traditional imaging techniques for the localization and monitoring of bacterial infections, although reasonably sensitive, suffer from a lack of specificity. This is particularly true for musculoskeletal infections. Bacteria possess a thymidine kinase (TK) whose substrate specificity is distinct from that of the major human TK. The substrate specificity difference has been exploited to develop a new imaging technique that can detect the presence of viable bacteria. METHODOLOGY/PRINCIPAL FINDINGS: Eight subjects with suspected musculoskeletal infections and one healthy control were studied by a combination of [(124)I]FIAU-positron emission tomography and CT ([(124)I]FIAU-PET/CT). All patients with proven musculoskeletal infections demonstrated positive [(124)I]FIAU-PET/CT signals in the sites of concern at two hours after radiopharmaceutical administration. No adverse reactions with FIAU were observed. CONCLUSIONS/SIGNIFICANCE: [(124)I]FIAU-PET/CT is a promising new method for imaging bacterial infections.Item Open Access Improving the rates of Aspergillus detection: an update on current diagnostic strategies.(Expert review of anti-infective therapy, 2019-01) Jenks, Jeffrey D; Salzer, Helmut JF; Hoenigl, MartinIntroduction
The spectrum of disease caused by Aspergillus spp. is dependent on the immune system of the host, and ranges from invasive aspergillosis (IA) to chronic pulmonary aspergillosis (CPA). Early and reliable diagnosis of Aspergillus disease is important to decrease associated morbidity and mortality. Areas covered: The following review will give an update on current diagnostic strategies for the diagnosis of IA and CPA. Expert commentary: Several new diagnostics for IA (including point-of-care tests) are now available to complement galactomannan testing. In particular, immunoPET/MRI imaging may be a promising approach for diagnosing IA in the near future. Notably, nearly all new biomarkers and tests for IA have been evaluated in the hematology setting only. Validation of biomarkers and tests is therefore needed for the increasing proportion of patients who develop IA outside the hematology setting. As an important first step, reliable definitions of IA are needed for non-hematology settings as clinical presentation and radiologic findings differ in these settings. CPA diagnosis is based on a combination of radiological findings in chest CT, mycological evidence (e.g. by the Aspergillus-specific IgG assay), exclusion of alternative diagnosis and chronicity. ([18F]FDG) PET/CT and immuno PET/MRI imaging are promising new imaging approaches.Item Open Access Increased Glutaminolysis Marks Active Scarring in Nonalcoholic Steatohepatitis Progression.(Cellular and molecular gastroenterology and hepatology, 2020-01) Du, Kuo; Chitneni, Satish K; Suzuki, Ayako; Wang, Ying; Henao, Ricardo; Hyun, Jeongeun; Premont, Richard T; Naggie, Susanna; Moylan, Cynthia A; Bashir, Mustafa R; Abdelmalek, Manal F; Diehl, Anna MaeBackground & aims
Nonalcoholic steatohepatitis (NASH) occurs in the context of aberrant metabolism. Glutaminolysis is required for metabolic reprograming of hepatic stellate cells (HSCs) and liver fibrogenesis in mice. However, it is unclear how changes in HSC glutamine metabolism contribute to net changes in hepatic glutaminolytic activity during fibrosis progression, or whether this could be used to track fibrogenic activity in NASH. We postulated that increased HSC glutaminolysis marks active scarring in NASH.Methods
Glutaminolysis was assessed in mouse NASH fibrosis models and in NASH patients. Serum and liver levels of glutamine and glutamate and hepatic expression of glutamine transporter/metabolic enzymes were correlated with each other and with fibrosis severity. Glutaminolysis was disrupted in HSCs to examine if this directly influenced fibrogenesis. 18F-fluoroglutamine positron emission tomography was used to determine how liver glutamine assimilation tracked with hepatic fibrogenic activity in situ.Results
The serum glutamate/glutamine ratio increased and correlated with its hepatic ratio, myofibroblast content, and fibrosis severity. Healthy livers almost exclusively expressed liver-type glutaminase (Gls2); Gls2 protein localized in zone 1 hepatocytes, whereas glutamine synthase was restricted to zone 3 hepatocytes. In fibrotic livers, Gls2 levels reduced and glutamine synthase zonality was lost, but both Slc1a5 (glutamine transporter) and kidney-type Gls1 were up-regulated; Gls1 protein was restricted to stromal cells and accumulated in fibrotic septa. Hepatocytes did not compensate for decreased Gls2 by inducing Gls1. Limiting glutamine or directly inhibiting GLS1 inhibited growth and fibrogenic activity in cultured human HSCs. Compared with healthy livers, fibrotic livers were 18F-fluoroglutamine-avid by positron emission tomography, suggesting that glutamine-addicted myofibroblasts drive increased hepatic utilization of glutamine as fibrosis progresses.Conclusions
Glutaminolysis is a potential diagnostic marker and therapeutic target during NASH fibrosis progression.Item Open Access Microdosing and drug development: past, present and future.(Expert Opin Drug Metab Toxicol, 2013-07) Lappin, Graham; Noveck, Robert; Burt, TalINTRODUCTION: Microdosing is an approach to early drug development where exploratory pharmacokinetic data are acquired in humans using inherently safe sub-pharmacologic doses of drug. The first publication of microdose data was 10 years ago and this review comprehensively explores the microdose concept from conception, over the past decade, up until the current date. AREAS COVERED: The authors define and distinguish the concept of microdosing from similar approaches. The authors review the ability of microdosing to provide exploratory pharmacokinetics (concentration-time data) but exclude microdosing using positron emission tomography. The article provides a comprehensive review of data within the peer-reviewed literature as well as the latest applications and a look into the future, towards where microdosing may be headed. EXPERT OPINION: Evidence so far suggests that microdosing may be a better predictive tool of human pharmacokinetics than alternative methods and combination with physiologically based modelling may lead to much more reliable predictions in the future. The concept has also been applied to drug-drug interactions, polymorphism and assessing drug concentrations over time at its site of action. Microdosing may yet have more to offer in unanticipated directions and provide benefits that have not been fully realised to date.Item Open Access Pilot Study of [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)/Magnetic Resonance Imaging (MRI) for Staging of Muscle-invasive Bladder Cancer (MIBC).(Clinical genitourinary cancer, 2020-10) Eulitt, Patrick J; Altun, Ersan; Sheikh, Arif; Wong, Terence Z; Woods, Michael E; Rose, Tracy L; Wallen, Eric M; Pruthi, Raj S; Smith, Angela B; Nielsen, Matthew E; Whang, Young E; Kim, William Y; Godley, Paul A; Basch, Ethan M; David, Grace U; Ramirez, Juanita; Deal, Allison M; Rathmell, W Kimryn; Chen, Ronald C; Bjurlin, Marc A; Lin, Weili; Lee, Joseph K; Milowsky, Matthew IIntroduction
Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [18F] Fluorodeoxyglucose positron emission tomography (FDG-PET)/magnetic resonance imaging (MRI) is a novel imaging modality incorporating functional imaging with improved soft tissue characterization. This pilot study evaluated the use of preoperative FDG-PET/MRI for staging of MIBC.Patients and methods
Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT).Results
Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology.Conclusions
This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC.Item Open Access Pitfalls of post-treatment PET after de-intensified chemoradiotherapy for HPV-associated oropharynx cancer: Secondary analysis of a phase 2 trial.(Oral oncology, 2018-03) Wang, Kyle; Wong, Terence Z; Amdur, Robert J; Mendenhall, William M; Sheets, Nathan C; Green, Rebecca; Thorp, Brian D; Patel, Samip N; Hackman, Trevor G; Zanation, Adam M; Weissler, Mark C; Chera, Bhishamjit SOBJECTIVES:We evaluated patterns of nodal response and positive predictive value (PPV) of 3 month post-treatment PET in patients with HPV-associated oropharyngeal cancer treated on a multi-institutional de-intensification trial. MATERIALS AND METHODS:Eligibility criteria included: (1) T0-3, N0-2c, M0, (2) HPV+/p16+ oropharyngeal squamous cell carcinoma, and (3) ≤10 pack-years smoking or ≤30 pack-years and abstinent ≥5 years. Patients received 60 Gy radiation alone (T0-2, N0-1) or with concurrent weekly cisplatin 30 mg/m2 and surveillance PET three months post-radiation. Nodal responses were categorized as complete (CR), equivocal (ER), or incomplete (IR) using both local and central radiographic review. A "true positive" was ER/IR with clinical/radiographic progression or positive pathology. RESULTS:79 node-positive pts (84% N2) were analyzed. Distribution of nodal CR, ER, and IR was 44 (56%), 27 (34%), and 8 (10%), respectively. 29 (37%) had ER/IR in pre-treatment node-positive neck levels, whereas 14 (18%) had ER/IR in pre-treatment node-negative levels. Of patients with ER/IR, 5 were observed clinically, 19 received repeat imaging, and 11 received either biopsy (1) or neck dissection (10). The PPV was 9% for ER/IR and 13% for IR, with 3 patients found to have persistent disease on neck dissection. There was no difference in nodal relapse rate in patients with nodal CR vs. nodal ER/IR. CONCLUSION:Post-treatment PET may not accurately predict the presence of persistent disease in patients with favorable-risk oropharynx cancer. These results support close surveillance rather than surgical evaluation in most favorable-risk patients.Item Open Access Quantitative imaging in oncology patients: Part 1, radiology practice patterns at major U.S. cancer centers.(AJR. American journal of roentgenology, 2010-07) Jaffe, Tracy A; Wickersham, Nicholas W; Sullivan, Daniel COBJECTIVE: The objective of our study was to examine radiologists' opinions and practice patterns concerning tumor measurements in cancer patients. MATERIALS AND METHODS: An electronic mail survey was sent to 565 abdominal imaging radiologists at 55 U.S. National Cancer Institute (NCI)-funded cancer centers. The survey contained questions about departmental demographics, procedures for interpretation of imaging in oncologic patients, and opinions concerning the role of radiologists in using the Response Evaluation Criteria in Solid Tumors (RECIST) system for tumor measurements. RESULTS: Two hundred ninety-six responses (52%) were received. The distribution of the size of the respondents' abdominal imaging groups was as follows: 1-5 (16/295, 5%), 6-10 (112/295, 38%), 11-15 (77/295, 26%), and > 20 (73/295, 25%). Most respondents dictate some but not all tumor measurements in the first clinical scan (236/270, 87%). For follow-up imaging, 95% (255/268) of respondents dictate tumor measurements for selected index lesions. Most respondents believe inclusion of tumor measurements in the first scan is the responsibility of the radiologist (248/262, 95%). Ninety percent of respondents (235/261) believe inclusion of several index lesion measurements is satisfactory to document disease activity. Eighty-two percent (214/260) of respondents were familiar with RECIST. Forty-two percent (110/262) of respondents' departments have a centralized process for approval of industry-sponsored oncologic trials in which imaging is an important component of the protocol end point. CONCLUSION: Most oncologic imaging at NCI-sponsored cancer centers includes tumor measurements on initial and follow-up imaging. Very few radiology departments have a centralized process for approval of clinical trial protocols that require imaging.Item Open Access Radiolabeled inhibitors as probes for imaging mutant IDH1 expression in gliomas: Synthesis and preliminary evaluation of labeled butyl-phenyl sulfonamide analogs.(Eur J Med Chem, 2016-08-25) Chitneni, Satish K; Reitman, Zachary J; Gooden, David M; Yan, Hai; Zalutsky, Michael RINTRODUCTION: Malignant gliomas frequently harbor mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Studies suggest that IDH mutation contributes to tumor pathogenesis through mechanisms that are mediated by the neomorphic metabolite of the mutant IDH1 enzyme, 2-hydroxyglutarate (2-HG). The aim of this work was to synthesize and evaluate radiolabeled compounds that bind to the mutant IDH1 enzyme with the goal of enabling noninvasive imaging of mutant IDH1 expression in gliomas by positron emission tomography (PET). METHODS: A small library of nonradioactive analogs were designed and synthesized based on the chemical structure of reported butyl-phenyl sulfonamide inhibitors of mutant IDH1. Enzyme inhibition assays were conducted using purified mutant IDH1 enzyme, IDH1-R132H, to determine the IC50 and the maximal inhibitory efficiency of the synthesized compounds. Selected compounds, 1 and 4, were labeled with radioiodine ((125)I) and/or (18)F using bromo- and phenol precursors, respectively. In vivo behavior of the labeled inhibitors was studied by conducting tissue distribution studies with [(125)I]1 in normal mice. Cell uptake studies were conducted using an isogenic astrocytoma cell line that carried a native IDH1-R132H mutation to evaluate the potential uptake of the labeled inhibitors in IDH1-mutated tumor cells. RESULTS: Enzyme inhibition assays showed good inhibitory potency for compounds that have iodine or a fluoroethoxy substituent at the ortho position of the phenyl ring in compounds 1 and 4 with IC50 values of 1.7 μM and 2.3 μM, respectively. Compounds 1 and 4 inhibited mutant IDH1 activity and decreased the production of 2-HG in an IDH1-mutated astrocytoma cell line. Radiolabeling of 1 and 4 was achieved with an average radiochemical yield of 56.6 ± 20.1% for [(125)I]1 (n = 4) and 67.5 ± 6.6% for [(18)F]4 (n = 3). [(125)I]1 exhibited favorable biodistribution characteristics in normal mice, with rapid clearance from the blood and elimination via the hepatobiliary system by 4 h after injection. The uptake of [(125)I]1 in tumor cells positive for IDH1-R132H was significantly higher compared to isogenic WT-IDH1 controls, with a maximal uptake ratio of 1.67 at 3 h post injection. Co-incubation of the labeled inhibitors with the corresponding nonradioactive analogs, and decreasing the normal concentrations of FBS (10%) in the incubation media substantially increased the uptake of the labeled inhibitors in both the IDH1-mutant and WT-IDH1 tumor cell lines, suggesting significant non-specific binding of the synthesized labeled butyl-phenyl sulfonamide inhibitors. CONCLUSIONS: These data demonstrate the feasibility of developing radiolabeled probes for the mutant IDH1 enzyme based on enzyme inhibitors. Further optimization of the labeled inhibitors by modifying the chemical structure to decrease the lipophilicity and to increase potency may yield compounds with improved characteristics as probes for imaging mutant IDH1 expression in tumors.Item Open Access Reply to "Prognostic Value of Fluorodeoxyglucose-Positron Emission Tomography".(J Thorac Oncol, 2015-10) Kwon, Woocheol; Howard, Brandon A; Herndon, James E; Patz, Edward FItem Open Access Task Group 174 Report: Utilization of [18 F]Fluorodeoxyglucose Positron Emission Tomography ([18 F]FDG-PET) in Radiation Therapy.(Medical physics, 2019-10) Das, Shiva K; McGurk, Ross; Miften, Moyed; Mutic, Sasa; Bowsher, James; Bayouth, John; Erdi, Yusuf; Mawlawi, Osama; Boellaard, Ronald; Bowen, Stephen R; Xing, Lei; Bradley, Jeffrey; Schoder, Heiko; Yin, Fang-Fang; Sullivan, Daniel C; Kinahan, PaulThe use of positron emission tomography (PET) in radiation therapy (RT) is rapidly increasing in the areas of staging, segmentation, treatment planning, and response assessment. The most common radiotracer is 18 F-fluorodeoxyglucose ([18 F]FDG), a glucose analog with demonstrated efficacy in cancer diagnosis and staging. However, diagnosis and RT planning are different endeavors with unique requirements, and very little literature is available for guiding physicists and clinicians in the utilization of [18 F]FDG-PET in RT. The two goals of this report are to educate and provide recommendations. The report provides background and education on current PET imaging systems, PET tracers, intensity quantification, and current utilization in RT (staging, segmentation, image registration, treatment planning, and therapy response assessment). Recommendations are provided on acceptance testing, annual and monthly quality assurance, scanning protocols to ensure consistency between interpatient scans and intrapatient longitudinal scans, reporting of patient and scan parameters in literature, requirements for incorporation of [18 F]FDG-PET in treatment planning systems, and image registration. The recommendations provided here are minimum requirements and are not meant to cover all aspects of the use of [18 F]FDG-PET for RT.