Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images

Purpose

Positron emission tomography (PET) with Zirconium-89 (Zr-89)-labeled antibodies can be used for in vivo quantification of antibody uptake. Knowledge about measurement variability is required to ensure correct interpretation. However, no clinical studies have been reported on measurement variability of Zr-89 immuno-PET. As variability due to low signal-to-noise is part of the total measurement variability, the aim of this study was to assess noise-induced variability of Zr-89 -immuno-PET using count-reduced clinical images.

Procedures

Data were acquired from three previously reported clinical studies with [⁸⁹Zr]antiCD20 (74 MBq, n?=?7), [⁸⁹Zr]antiEGFR (37 MBq, n?=?7), and [⁸⁹Zr]antiCD44 (37 MBq, n?=?13), with imaging obtained 1 to 6 days post injection (D0–D6). Volumes of interest (VOIs) were manually delineated for liver, spleen, kidney, lung, brain, and tumor. For blood pool and bone marrow, fixed-size VOIs were used. Original PET list mode data were split and reconstructed, resulting in two count-reduced images at 50 % of the original injected dose (e.g., 37 MBq_74inj).Repeatability coefficients (RC) were obtained from Bland-Altman analysis on standardized uptake values (SUV) derived from VOIs applied to these images.

Results

The RC for the combined manually delineated organs for [⁸⁹Zr] antiCD20 (37 MBq_74inj) increased from D0 to D6 and was less than 6 % at all time points. Blood pool and bone marrow had higher RC, up to 43 % for 37 MBq_74inj at D6. For tumor, the RC was up to 42 % for [⁸⁹Zr]antiCD20 (37 MBq_74inj). For [⁸⁹Zr]antiCD20, (18 MBq_74inj), [⁸⁹Zr]antiEGFR (18 MBq_37inj), and [⁸⁹Zr]antiCD44 (18 MBq_37inj), measurement variability was independent of the investigated antibody.

Conclusions

Based on this study, noise-induced variability results in a RC for Zr-89-immuno-PET (37 MBq) around 6 % for manually delineated organs combined, increasing up to 43 % at D6 for blood pool and bone marrow, assuming similar biodistribution of antibodies. The signal-to-noise ratio leads to tumor RC up to 42 %.

     

Combined Efficacy of Acamprosate and Disulfiram in the Treatment of Alcoholism: A Controlled Study

This study presents the results of a multicenter investigation of the efficacy of acamprosate in the treatment of patients with chronic or episodic alcohol dependence. One hundred eighteen patients were randomly assigned to either placebo or acamprosate, and both groups were stratified for concomitant voluntary use of disulfiram. Treatment lasted for 380 days, with an additional 360-day follow-up period. The primary efficacy parameters evaluated were: relapse rate and cumulative abstinence duration (CAD). Results were analyzed according to Intention-To-Treat principles using χ², t , and multiple regression analyses where appropriate. After 30 days on study medication, 40 of 55 (73%) acamprosate-treated patients were abstinent, compared with 26 of 55 (43%) placebo-treated patients ( p = 0.019). The treatment advantage remained throughout the study medication period and was statistically significant until day 270 ( p = 0.028). Twenty-seven percent of patients on acamprosate and 53% of patients on placebo had a first drink within the first 30 days of the study. The mean CAD was 137 days (40% abstinent days) for the patients treated with acamprosate and 75 days (21% abstinent days) for the placebo group ( p = 0.013). No adverse interaction between acamprosate and disulfiram occurred, and the subgroup who received both medications had a better outcome on CAD than the those on only one or no medication. Acamprosate was well tolerated. Diarrhea was the only significant treatment-induced effect. It was concluded that acamprosate was a useful and safe pharmacotherapy in the long-term treatment of alcoholism. Concomitant administration of disulfiram improved the effectiveness of acamprosate.     

The use of an implantable loop recorder in the investigation of unexplained syncope in older people

INTRODUCTION: Reveal is a patient activated implantable loop recorder device with an 18 month battery life now available to assist in the diagnosis of suspected syncope or arrhythmias. We present our experience using this device in older subjects referred to a dedicated falls and syncope clinic in whom usual clinical assessment had not satisfactorily identified an attributable diagnosis but where we still suspected a cardiovascular cause for syncope or falls. METHODS AND RESULTS: during the past 3 years 15 subjects (mean age 73 years, range 61-89 years) had Reveal implanted for symptoms of syncope alone (n=6; 40%) and unexplained falls (n=3; 20%) or symptoms of syncope and unexplained falls (n=6; 40%). Symptom duration was long (mean 48 months; range 4-200 months). Subjects had experienced significant morbidity, 6 subjects (40%) required A&E attendance or hospital admission and 4 (27%) experienced a fracture. Despite extensive and repeated investigations, which included 12-lead ECG, echocardiogram, 24-h ambulatory heart rate monitor, 24-h ambulatory blood pressure monitor, orthostatic blood pressure measurement, supine and erect carotid sinus massage, electroencephalogram, and passive and GTN head up tilt testing, the attributable diagnosis remained unexplained. Of the 15 subjects, 7 have activated the device at 4 (range 0-14) months after implantation. Bradycardia was identified in 3 and ventricular tachycardia in 1 subject. Two subjects did not activate the device during the 18 months it was in-situ. Four people had problems with device activation. This is comparable to rates noted using Reveal in younger subjects. CONCLUSION: Reveal offers additional diagnostic yield in complex elderly subjects with suspected cardiovascular causes of syncope or unexplained falls which have not been previously satisfactorily diagnosed despite extensive investigations.     

Diversity of Culex torrentium Martini, 1925 — a potential vector of arboviruses and filaria in Europe

Culex torrentium is one of the most common mosquito species in Germany. Due to its sympatric occurrence as well as its similar morphological and ecological characteristics, it has often been confused with another common species, Culex pipiens. Both species are known to be potential vectors for different arboviruses (not only in Germany) with C. torrentium being a possible vector for Sindbis or Ockelbo virus. In our study, we analyzed the genetic variability in a 658 bp fragment of the cytochrome c oxidase subunit I gene (coxI) of C. torrentium, from nine localities in the Frankfurt/Rhine-Main Metropolitan Region. The results of our genetic survey indicate a higher genetic diversity in this gene region for C. torrentium than for the morphologically similar C. pipiens. Our findings may explain the difficulties in the past to find morphological characteristics that apply to all populations of C. torrentium, when attempting to separate them clearly from C. pipiens, by any other criteria than male genitalia. Being ornithophilic, possible hybrids between C. torrentium and the humanophilic C. pipiens biotype molestus, could potentially serve as important vectors for zoonotic diseases. Therefore, we recommend that greater emphasis is placed on the ecological characteristics, population structure, and the taxonomy of this often neglected species, in the future.     

Artificial Intelligence for Fast and Accurate 3-Dimensional Tooth Segmentation on Cone-beam Computed Tomography

IntroductionTooth segmentation on cone-beam computed tomographic (CBCT) imaging is a labor-intensive task considering the limited contrast resolution and potential disturbance by various artifacts. Fully automated tooth segmentation cannot be achieved by merely relying on CBCT intensity variations. This study aimed to develop and validate an artificial intelligence (AI)-driven tool for automated tooth segmentation on CBCT imaging.MethodsA total of 433 Digital Imaging and Communications in Medicine images of single- and double-rooted teeth randomly selected from 314 anonymized CBCT scans were imported and manually segmented. An AI-driven tooth segmentation algorithm based on a feature pyramid network was developed to automatically detect and segment teeth, replacing manual user contour placement. The AI-driven tool was evaluated based on volume comparison, intersection over union, the Dice score coefficient, morphologic surface deviation, and total segmentation time.ResultsOverall, AI-driven and clinical reference segmentations resulted in very similar segmentation volumes. The mean intersection over union for full-tooth segmentation was 0.87 (±0.03) and 0.88 (±0.03) for semiautomated (SA) (clinical reference) versus fully automated AI-driven (F-AI) and refined AI-driven (R-AI) tooth segmentation, respectively. R-AI and F-AI segmentation showed an average median surface deviation from SA segmentation of 9.96 μm (±59.33 μm) and 7.85 μm (±69.55 μm), respectively. SA segmentations of single- and double-rooted teeth had a mean total time of 6.6 minutes (±76.15 seconds), F-AI segmentation of 0.5 minutes (±8.64 seconds, 12 times faster), and R-AI segmentation of 1.2 minutes (±33.02 seconds, 6 times faster).ConclusionsThis study showed a unique fast and accurate approach for AI-driven automated tooth segmentation on CBCT imaging. These results may open doors for AI-driven applications in surgical and treatment planning in oral health care.     

Effect of Plaque Burden and Morphology on Myocardial Blood Flow and Fractional Flow Reserve

Background

Atherosclerotic plaque characteristics may affect downstream myocardial perfusion, as well as coronary lesion severity.