Assessing and reducing PET radiotracer infiltration rates: a single center experience in injection quality monitoring methods and quality improvement.

BACKGROUND: Successful injection of radiolabeled compounds is critical for positron emission tomography (PET) imaging. A poor quality injection limits the tracer availability in the body and can impact diagnostic results. In this study, we attempt to quantify our infiltration rates, develop an actionable quality improvement plan to reduce potentially compromised injections, and compare injection scoring to PET/CT imaging results. METHODS: A commercially available system that uses external radiation detectors was used to monitor and score injection quality. This system compares the time activity curves of the bolus relative to a control reading in order to provide a score related to the quality of the injection. These injection scores were used to assess infiltration rates at our facility in order to develop and implement a quality improvement plan for our PET imaging center. Injection scores and PET imaging results were reviewed to determine correlations between image-based assessments of infiltration, such as liver SUVs, and injection scoring, as well as to gather infiltration reporting statistics by physicians. RESULTS: A total of 1033 injections were monitored at our center. The phase 1 infiltration rate was 2.1%. In decision tree analysis, patients < 132.5lbs were associated with infiltrations. Additional analyses suggested patients > 127.5 lbs. with non-antecubital injections were associated with lower quality injections. Our phase 2 infiltration rate was 1.9%. Comparison of injection score to SUV showed no significant correlation and indicated that only 63% of suspected infiltrations were visible on PET/CT imaging. CONCLUSIONS: Developing a quality improvement plan and monitoring PET injections can lead to reduced infiltration rates. No significant correlation between reference SUVs and injection score provides evidence that determination of infiltration based on PET images alone may be limited. Results also indicate that the number of infiltrated PET injections is under-reported.

A two-branch cloud detection algorithm based on the fusion of a feature enhancement module and Gaussian mixture model.

Accurate cloud detection is an important step to improve the utilization rate of remote sensing (RS). However, existing cloud detection algorithms have difficulty in identifying edge clouds and broken clouds. Therefore, based on the channel data of the Himawari-8 satellite, this work proposes a method that combines the feature enhancement module with the Gaussian mixture model (GMM). First, statistical analysis using the probability density functions (PDFs) of spectral data from clouds and underlying surface pixels was conducted, selecting cluster features suitable for daytime and nighttime. Then, in this work, the Laplacian operator is introduced to enhance the spectral features of cloud edges and broken clouds. Additionally, enhanced spectral features are input into the debugged GMM model for cloud detection. Validation against visual interpretation shows promising consistency, with the proposed algorithm outperforming other methods such as RF, KNN and GMM in accuracy metrics, demonstrating its potential for high-precision cloud detection in RS images.

Radioimmunodetection of amyloid deposits in patients with AL amyloidosis.

Care of patients with AL amyloidosis currently is limited by the lack of objective means to document disease extent, as well as therapeutic options that expedite removal of pathologic deposits. To address these issues, we have initiated a Phase I Exploratory IND study to determine the biodistribution of the fibril-reactive, amyloidolytic murine IgG1 mAb 11-1F4 labeled with I-124. Patients were infused with less than 1 mg (∼ 74 MBq) of GMP-grade antibody and imaged by PET/CT scan 48 and 120 hours later. Among 9 of 18 subjects, there was striking uptake of the reagent in liver, lymph nodes, bone marrow, intestine, or, unexpectedly, spleen (but not kidneys or heart). Generally, positive or negative results correlated with those obtained immunohistochemically using diagnostic tissue biopsy specimens. Based on these findings, we posit that (124)I-mAb m11-1F4 can be used to identify AL candidates for passive immunotherapy using the chimeric form of the antibody.

Fibrolipomatous hamartoma of the inferior calcaneal nerve (Baxter nerve).

Fibrolipomatous hamartoma (FLH) is a rare, benign lesion of the peripheral nerves most frequently involving the median nerve and its digital branches (80 %). Pathognomonic MR features of FLH such as coaxial-cable-like appearance on axial planes and a spaghetti-like appearance on coronal planes have been described by Marom and Helms, obviating the need for diagnostic biopsy. We present a case of fibrolipomatous hamartoma of the inferior calcaneal nerve (Baxter nerve) with associated subcutaneous fat proliferation.

Data-driven head motion correction for PET using time-of-flight and positron emission particle tracking techniques.

OBJECTIVES: Positron emission tomography (PET) is susceptible to patient movement during a scan. Head motion is a continuing problem for brain PET imaging and diagnostic assessments. Physical head restraints and external motion tracking systems are most commonly used to address to this issue. Data-driven methods offer substantial advantages, such as retroactive processing but typically require manual interaction for robustness. In this work, we introduce a time-of-flight (TOF) weighted positron emission particle tracking (PEPT) algorithm that facilitates fully automated, data-driven head motion detection and subsequent automated correction of the raw listmode data. MATERIALS METHODS: We used our previously published TOF-PEPT algorithm Dustin Osborne et al. (2017), Tasmia Rahman Tumpa et al., Tasmia Rahman Tumpa et al. (2021) to automatically identify frames where the patient was near-motionless. The first such static frame was used as a reference to which subsequent static frames were registered. The underlying rigid transformations were estimated using weak radioactive point sources placed on radiolucent glasses worn by the patient. Correction of raw event data were achieved by tracking the point sources in the listmode data which was then repositioned to allow reconstruction of a single image. To create a "gold standard" for comparison purposes, frame-by-frame image registration based correction was implemented. The original listmode data was used to reconstruct an image for each static frame detected by our algorithm and then applying manual landmark registration and external software to merge these into a single image. RESULTS: We report on five patient studies. The TOF-PEPT algorithm was configured to detect motion using a 500 ms window. Our event-based correction produced images that were visually free of motion artifacts. Comparison of our algorithm to a frame-based image registration approach produced results that were nearly indistinguishable. Quantitatively, Jaccard similarity indices were found to be in the range of 85-98% for the former and 84-98% for the latter when comparing the static frame images with the reference frame counterparts. DISCUSSION: We have presented a fully automated data-driven method for motion detection and correction of raw listmode data. Easy to implement, the approach achieved high temporal resolution and reliable performance for head motion correction. Our methodology provides a mechanism by which patient motion incurred during imaging can be assessed and corrected post hoc.

The Scientific and Clinical Case for Reviewing Diagnostic Radiopharmaceutical Extravasation Long-Standing Assumptions.

Background: The patient benefit from a diagnostic nuclear medicine procedure far outweighs the associated radiation risk. This benefit/risk ratio assumes a properly administered radiopharmaceutical. However, a significant diagnostic radiopharmaceutical extravasation can confound the procedure in many ways. We identified three current extravasation hypotheses espoused by medical societies, advisory committees, and hundreds of individual members of the nuclear medicine community: diagnostic extravasations do not cause harm, do not result in high absorbed dose to tissue, and require complex dosimetry methods that are not readily available in nuclear medicine centers. We tested these hypotheses against a framework of current knowledge, recent developments, and original research. We conducted a literature review, searched regulatory databases, examined five clinical cases of extravasated patients, and performed dosimetry on those extravasations to test these globally accepted hypotheses. Results: A literature review found 58 peer-reviewed documents suggesting patient harm. Adverse event/vigilance report database reviews for extravasations were conducted and revealed 38 adverse events which listed diagnostic radiopharmaceutical extravasation as a factor, despite a regulatory exemption for required reporting. In our own case material, assessment of care was evaluated for five extravasated patients who underwent repeat imaging. Findings reflected results of literature review and included mis- or non-identification of lesions, underestimation of Standardized Uptake Values (SUVs) by 19-73%, classification of scans as non-diagnostic, and the need to repeat imaging with the associated additional radiation exposure, inconvenience, or delays in care. Dosimetry was performed for the same five cases of diagnostic radiopharmaceutical extravasation. Absorbed doses to 5 cm3 of tissue were between 1.1 and 8.7 Gy, and shallow dose equivalent for 10 cm2 of skin was as high as 4.2 Sv. Conclusions: Our findings suggest that significant extravasations can or have caused patient harm and can irradiate patients' tissue with doses that exceed medical event reporting limits and deterministic effect thresholds. Therefore, diagnostic radiopharmaceutical injections should be monitored, and dosimetry of extravasated tissue should be performed in certain cases where thresholds are thought to have been exceeded. Process improvement efforts should be implemented to reduce the frequency of extravasation in nuclear medicine.

Chronic nicotine self-administration augments hypothalamic-pituitary-adrenal responses to mild acute stress.

We investigated the effect of chronic nicotine self-administration (SA) on hypothalamic-pituitary-adrenal (HPA) hormonal responses to acute stressors. Adult male Sprague-Dawley rats were given access to nicotine (0.03 mg/kg) for 23 h per day for 20 days. On day 1 of acquisition of nicotine SA, plasma levels of both adrenocorticotropin and corticosterone were significantly increased 15-30 min after the first dose of nicotine. These hormonal changes were no longer significant on day 3, when adrenocorticotropin levels were <60 pg/ml and corticosterone levels were <110 ng/ml during the hour after the first dose of nicotine. Chronic nicotine SA (20 days) significantly augmented (2-3-fold) both hormonal responses to mild foot shock stress (0.6 mA, 0.5 s per shock, 5 shocks per 5 min), but did not affect hormonal responses to moderate shock (1.2 mA, 0.5 s per shock, 5 shocks per 5 min), lipopolysaccharide or immobilization. Similar data were obtained in Lewis rats. These results provide further support for the concept that chronic nicotine SA is a stressor. In alignment with the effects of other stressors, nicotine activated the HPA axis on the first day of SA, but desensitization occurred with repeated exposure. Furthermore, chronic nicotine SA selectively cross-sensitized the HPA response to a novel stressor. These observations suggest that nicotine may selectively increase the HPA response to stressors in human smokers.

Feasibility assessment of yttrium-90 liver radioembolization imaging using amplitude-based gated PET/CT.

PURPOSE: The usage of PET/computed tomography (CT) to monitor hepatocellular carcinoma patients following yttrium-90 (Y) radioembolization has increased. Respiratory motion causes liver movement, which can be corrected using gating techniques at the expense of added noise. This work examines the use of amplitude-based gating on Y-PET/CT and its potential impact on diagnostic integrity. PATIENTS AND METHODS: Patients were imaged using PET/CT following Y radioembolization. A respiratory band was used to collect respiratory cycle data. Patient data were processed as both standard and motion-corrected images. Regions of interest were drawn and compared using three methods. Activity concentrations were calculated and converted into dose estimates using previously determined and published scaling factors. Diagnostic assessments were performed using a binary scale created from published Y-PET/CT image interpretation guidelines. RESULTS: Estimates of radiation dose were increased (P<0.05) when using amplitude-gating methods with Y PET/CT imaging. Motion-corrected images show increased noise, but the diagnostic determination of success, using the Kao criteria, did not change between static and motion-corrected data. CONCLUSION: Amplitude-gated PET/CT following Y radioembolization is feasible and may improve Y dose estimates while maintaining diagnostic assessment integrity.

90Y Liver Radioembolization Imaging Using Amplitude-Based Gated PET/CT.

The usage of PET/CT to monitor patients with hepatocellular carcinoma following Y radioembolization has increased; however, image quality is often poor because of low count efficiency and respiratory motion. Motion can be corrected using gating techniques but at the expense of additional image noise. Amplitude-based gating has been shown to improve quantification in FDG PET, but few have used this technique in Y liver imaging. The patients shown in this work indicate that amplitude-based gating can be used in Y PET/CT liver imaging to provide motion-corrected images with higher estimates of activity concentration that may improve posttherapy dosimetry.

Norepinephrine release in amygdala of rats during chronic nicotine self-administration: an in vivo microdialysis study.

The essential role of the amygdala in learning and memory, including cue-associated learning, is influenced by local release of norepinephrine (NE). The current study investigated changes in amygdaloid NE secretion in rats learning to self-administer nicotine in an unlimited access model (23 h/day). In vivo microdialysis of NE was performed for 9 h intervals during three phases of nicotine self-administration: acquisition (day 1); early maintenance, when self-administration rates first stabilized (day 8.4+/-0.7); and later, during fully stable maintenance (day 17.6+/-1.0). On day 1, a greater number of self-administration episodes (SAEs) were associated with elevated NE levels in rats bar-pressing for nicotine (88% vs. 39% with saline). By early maintenance, such episodes increased threefold and overall NE levels were greater. During later maintenance, however, bar-pressing behavior was similar and NE was elevated by the first SAE of the day, but total daily NE levels were no longer elevated. In all the three phases, the enhanced NE release during the first daily SAE did not occur in the last SAE 9 h later. Thus, in an animal model of unlimited nicotine self-administration that approximates the human pattern of nicotine consumption via smoking, the amygdaloid NE response to nicotine diminishes over each day and with the stabilization of self-administration. The decline of amygdaloid NE secretion after long-term nicotine self-administration likely reflects desensitization to the pharmacological effects of nicotine. In addition, amygdaloid NE release, which enhances the consolidation of amygdala-dependent memory, may no longer be necessary once self-administration behavior has been established.

Rat strain differences in nicotine self-administration using an unlimited access paradigm.

An effective animal model for elucidating the neurobiological basis of human smoking should simulate important aspects of this behavior. Therefore, a 23 h unlimited access nicotine self-administration model was used to compare inbred Lewis rats, which have a propensity to self-administer drugs of abuse, to inbred Fisher 344 rats and to the outbred Holtzman strain. Using this unlimited access model, 88.8% of Lewis vs. 57.1% of Holtzman rats achieved maintenance self-administration at a fixed ratio 1 (FR 1) at 0.03 mg/kg IV nicotine (P<0.05). In contrast, Fisher rats did not acquire self-administration under these conditions. Of the Lewis and Holtzman rats that achieved maintenance self-administration on an FR 1 schedule, a greater percentage of Lewis rats acquired nicotine self-administration at FR 2 (P<0.05) and progressed to FR 4 (P<0.05). Using naïve cohorts in a progressive dose reduction study, 83.3% of Lewis rats achieved maintenance at 0.0075 mg/kg nicotine as compared to 31.8% of Holtzman rats (P<0.05). Furthermore, only Lewis rats showed differences in active vs. inactive bar presses during maintenance at sequential dose reductions (P<0.001). Thus, in this unlimited access model, inbred Lewis rats will more reliably acquire nicotine self-administration than outbred Holtzman rats. Moreover, Lewis rats showed a significantly higher likelihood of continuing to self-administer nicotine in face of both increasing work requirements and decreasing drug reinforcement. Therefore, it is likely that Lewis rats would be genetically susceptible to nicotine addiction.

Effects of galantamine, a nicotinic allosteric potentiating ligand, on nicotine-induced catecholamine release in hippocampus and nucleus accumbens of rats.

Galantamine, a drug for treatment of Alzheimer's disease, is a novel cholinergic agent with a dual mode of action that inhibits acetylcholinesterase and allosterically modulates nicotinic cholinergic receptors (nAChRs). Nicotine stimulates catecholamine secretion, inducing hippocampal norepinephrine (NE) release, and improves memory consolidation. Thus, the effect of galantamine on nicotine-induced hippocampal NE secretion was investigated. This was compared with the effect of galantamine on nicotine-induced dopamine (DA) release within the nucleus accumbens of the same rat. Nicotine (0.025-0.09 mg/kg i.v.) dose dependently increased NE and DA levels in microdialysates from the hippocampus and nucleus accumbens, respectively, of freely moving rats. Pretreatment with galantamine (3.0 mg/kg s.c.) 3 h before nicotine either potentiated NE responses to doses of nicotine that were ineffective alone (0.025-0.045 mg/kg) or significantly enhanced (0.065 mg/kg) NE responses, whereas galantamine was ineffective when administered 2 or 4 h before nicotine. In contrast to its effects on NE, galantamine did not alter accumbal DA responses to any dose of nicotine. These selective effects of galantamine on nicotine-stimulated NE secretion may reflect differences in local neural circuits that use nAChRs to modulate hippocampal NE versus accumbal DA release.

Gestational nicotine exposure attenuates nicotine-stimulated dopamine release in the nucleus accumbens shell of adolescent Lewis rats.

The effects of chronic gestational exposure to nicotine on the nucleus accumbens dopamine response to acute nicotine were determined during adolescence (postnatal day 29-36) in cross-fostered and noncross-fostered Lewis rats. In both males and females, gestational nicotine exposure diminished the adolescent nucleus accumbens dopamine response to 0.07 mg/kg nicotine i.v. (p < 0.05). However, dopamine responses to 0.105 mg/kg nicotine were unaffected by gestational nicotine treatment and were similar in both genders. Furthermore, in both female and male gestational nicotine and control groups, the dopamine response to nicotine (0.105) was the same as that observed to the lower dose of nicotine in gestational controls. Thus, in adolescent male and female Lewis rats, gestational nicotine exposure attenuated nucleus accumbens dopamine release to a maximally stimulative dose of nicotine. Unexpectedly, in female gestational controls cross-fostering per se reduced nucleus accumbens dopamine secretion to 0.07 mg/kg nicotine (p < 0.05). These investigations suggest that gestational nicotine exposure could modify the acute reinforcing effects of nicotine in adolescent rats, whereas early postnatal stressors, (e.g., cross-fostering) may affect nicotine-induced reinforcement in female but not male adolescents.

Up-regulation of brain nicotinic acetylcholine receptors in the rat during long-term self-administration of nicotine: disproportionate increase of the alpha6 subunit.

In male rats continually self-administering nicotine (approximately 1.5 mg free base/kg/day), we found a significant increase of nicotinic acetylcholine receptors (nAChRs) labeled by epibatidine (Epb) in 11 brain areas. A large increase of high-affinity Epb binding sites was apparent in the ventral tegmentum/substantia nigra, nucleus tractus solitarii, nucleus accumbens, thalamus/subthalamus, parietal cortex, hypothalamus, and amygdala. A smaller but significant up-regulation of high-affinity Epb sites was seen in the piriform cortex, hippocampus, caudate/putamen, and cerebellar cortex. The up-regulation of nAChRs, shown by immunoadsorption and Western blotting, involved alpha4, alpha6, and beta2 subunits. As a consequence of long-term self-administration of nicotine, the alpha6 immunoreactive (IR) binding of either labeled Epb or 125I-alpha-conotoxin MII increased to a much greater extent than did alpha4 or beta2 IR binding of Epb. In addition, the beta2 IR binding of Epb was consistently enhanced to a greater extent than was alpha4. These findings may reflect a larger surface membrane retention of alpha6-containing and, to some degree, beta2-containing nAChRs compared with alpha4-containing nAChRs during long-term self-administration of nicotine.