Nanosponges: As a Dynamic Drug Delivery Approach for Targeted Delivery

Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.

Ultrahigh-Resolution Photon-Counting Detector CT of the Lungs: Association of Reconstruction Kernel and Slice Thickness With Image Quality.

BACKGROUND. Prior work has shown improved image quality for photon-counting detector (PCD) CT of the lungs compared with energy-integrating detector CT. A paucity of the literature has compared PCD CT of the lungs using different reconstruction parameters. OBJECTIVE. The purpose of this study is to the compare the image quality of ultra-high-resolution (UHR) PCD CT image sets of the lungs that were reconstructed using different kernels and slice thicknesses. METHODS. This retrospective study included 29 patients (17 women and 12 men; median age, 56 years) who underwent noncontrast chest CT from February 15, 2022, to March 15, 2022, by use of a commercially available PCD CT scanner. All acquisitions used UHR mode (1024 × 1024 matrix). Nine image sets were reconstructed for all combinations of three sharp kernels (BI56, BI60, and BI64) and three slice thicknesses (0.2, 0.4, and 1.0 mm). Three radiologists independently reviewed reconstructions for measures of visualization of pulmonary anatomic structures and pathologies; reader assessments were pooled. Reconstructions were compared with the clinical reference reconstruction (obtained using the BI64 kernel and a 1.0-mm slice thickness [BI641.0-mm]). RESULTS. The median difference in the number of bronchial divisions identified versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.5), BI600.4-mm (0.3), BI640.2-mm (0.5), and BI600.2-mm (0.2) (all p < .05). The median bronchial wall sharpness versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.3) and BI640.2-mm (0.3) and was lower for BI561.0-mm (-0.7) and BI560.4-mm (-0.3) (all p < .05). Median pulmonary fissure sharpness versus the clinical reference reconstruction was higher for reconstructions with BI640.4-mm (0.3), BI600.4-mm (0.3), BI560.4-mm (0.5), BI640.2-mm (0.5), BI600.2-mm (0.5), and BI560.2-mm (0.3) (all p < .05). Median pulmonary vessel sharpness versus the clinical reference reconstruction was lower for reconstructions with BI561.0-mm (-0.3), BI600.4-mm (-0.3), BI560.4-mm (-0.7), BI640.2-mm (-0.7), BI600.2-mm (-0.7), and BI560.2-mm (-0.7). Median lung nodule conspicuity versus the clinical reference reconstruction was lower for reconstructions with BI561.0-mm (-0.3) and BI560.4-mm (-0.3) (both p < .05). Median conspicuity of all other pathologies versus the clinical reference reconstruction was lower for reconstructions with BI561.0 mm (-0.3), BI560.4-mm (-0.3), BI640.2-mm (-0.3), BI600.2-mm (-0.3), and BI560.2-mm (-0.3). Other comparisons among reconstructions were not significant (all p > .05). CONCLUSION. Only the reconstruction using BI640.4-mm yielded improved bronchial division identification and bronchial wall and pulmonary fissure sharpness without a loss in pulmonary vessel sharpness or conspicuity of nodules or other pathologies. CLINICAL IMPACT. The findings of this study may guide protocol optimization for UHR PCD CT of the lungs.

How did the COVID-19 pandemic affect SPECT myocardial perfusion scans?

Objectives: The aim of this study is to evaluate the effect of the COVID-19 pandemic on myocardial perfusion scans (MPS) during the COVID-19 pandemic period. Method(s): We respectively reviewed single photon emission computed tomography myocardial perfusion scans (SPECT-MPS) performed between June and September 2020 during the COVID-19 pandemic at the Nuclear Medicine Research Center at Mashhad University of Medical Sciences. The findings of stress SPECT-MPS studies acquired in the corresponding months of 2019 were also evaluated for direct comparison. Result(s): In COVID-19 pandemic compared to period prior to the pandemic, no difference was observed in terms of age range of patients under study or their cardiovascular risk factors, except smoking which underwent a significant increase during the COVID-19 pandemic ( 19% vs. 13% , p = 0.009). While the number of patients with non-angina (19% vs. 31%, p = 0.000) or typical (11% vs. 19%, p = 0.000) chest pain significantly decreased during the COVID-19 pandemic, atypical (42% vs. 25%, p = 0.000) chest pain cases showed an increasing number. By considering pretest probability of the patients (high, intermediate and low/very low), during the COVID-19 period, cases of high pretest probability decreased (6% vs. 18%, p = 0.000) and intermediate pretest probability patients also increased (64% vs. 55%, p = 0.005) while low/very low pretest probability cases showed no changes between the two periods. All types of MPS stress tests in the COVID-19 period were pharmacological compared to exercise stress test. No statistically significant difference on the myocardial ischemia or cardiomyopathy between patients between the two periods was observed. Summed stress score (SSS) and summed rest score (SRS) was similar over the two periods,while summed difference score (SDS) significantly increased over the course of COVID-19, confirming a non- increasing pattern of myocardial ischemia. Conclusion(s): Previous research underscores the fact that the number of stress SPECT-MPS studies was significantly reduced during the COVID-19 pandemic compared to the corresponding months prior to the pandemic [1, 2]. Our study concluded that all types of MPS stress tests in the COVID-19 period were pharmacological. This is due to the fact that all related recommendations published in the literature [3] highlighted the avoidance of exercise stress tests during the COVID-19 pandemic to reduce the risk of droplet exposure. During the COVID-19 pandemic, patients in two ends of the spectrum (e.g., non-angina & typical chest pain) were referred less for MPS. However, patients in the middle of the spectrum (e.g., atypical chest pain) underwentMPS less frequently. Myocardial ischemia and cardiomyopathy were not decreased or increased in patients over the COVID-19 period.

American College of Nuclear Medicine (ACNM) 2022 ACNM Annual Meeting Abstracts

The proceedings contain 91 papers. The topics discussed include: the new approach of COVID-19 patients with deteriorating respiratory functions using perfusion SPECT/CT imaging;increasing interest in nuclear medicine: evaluation of an educational workshop;cost-benefit analysis recommends further utilization of cardiac PET/MR for sarcoidosis evaluation;development of a nomogram model for predicting the recurrence of differentiated thyroid carcinoma patients based on a thyroid cancer database from a tertiary hospital in China;multi-center validation of radiomic models in new data using ComBat-based harmonization of features;bone scan with Tc99m-MDP, the missing link in the initial staging of muscle-invasive bladder carcinoma;and comparison of absorbed doses to kidneys calculated employing three time points and employing two time points in neuroendocrine patients undergoing Lu-177 DOTATATE therapy using planar images.

Ventilation Perfusion Functional Difference Images in Lung Spect: A Quantitative Improvement on Ventilation Perfusion Ratio

Purpose: Ventilation (V) perfusion (Q) SPECT imaging is important in the diagnostics of lung diseases such as pulmonary embolism, chronic obstructive pulmonary disease and recently in COVID-19 lung disease. The combined assessment of ventilation and perfusion permits the identification of classical mismatched and reverse mismatched defects, especially when these two parameters are combined in one measure as the ventilation perfusion ratio. Unfortunately, the ratio is only linear for ventilation and the scale is not symmetrical regarding classical and reversed mismatches. Small perfusion values give rise to artifacts. The scaled ventilation perfusion difference is presented as an alternative. Material(s) and Method(s): VQ SPECT was performed on patients with and without defects. Kr-81m was used as a ventilation tracer and MAA labelled with Tc-99m as a perfusion tracer. Ratio is defined as V/kQ and difference as V-kQ, where k is a scaling factor. The iterative z-map method was applied for determining the scaling factor for ratio and difference images yielding a ratio of one and zero difference for matched ventilation and perfusion. Clinical thresholds for both the difference images are derived resulting in color maps of relevant mismatches with an absolute ratio larger than the arbitrary value of two. Result(s): The relative difference is in second order proportional to the logarithm of the ratio, and has a scale going from -1 to +1, where -1 is perfusion only and +1 is ventilation only. Still the diagnostic value is hampered by the fact that areas with both low perfusion and ventilation can have high ratios. Therefore, the scaled (functional) difference is presented. Ratio, relative difference and scaled difference have been investigated in ten patients and are shown for three patients (one without defects). Ratio and relative difference images suffer from a visual overexposure effect as is clearly visible for the respiratory tract. One patient with an area in a bottom lung with a very low perfusion and slightly decreased ventilation demonstrated overflow problems of the intensity in ratio images and an overestimation of the mismatched area in both the ratio and relative difference images. Conclusion(s): While the relative ventilation perfusion-difference is a promising improvement of the ventilation-perfusion ratio, because it has a symmetrical scale and is bound on a closed domain, a better diagnostic value and functionality might be obtained by utilizing the scaled functional difference. The latter one seems superior to both the relative difference and ratio.Copyright © 2023 Southern Society for Clinical Investigation.

Development of an Ictal Spect Service for Irish Epilepsy Patients

Purpose: Beaumont Hospital (Dublin) is a large academic teaching hospital and specialist centre for complex epilepsy and epilepsy surgery. Ictal SPECT is a unique Nuclear Medicine examination that can be used as a tool in pre-surgical localisation of an epileptic focus. During a seizure there is hyper perfusion in the epileptogenic focus. While the patient is being EEG monitored in the Epilepsy Monitoring Unit (EMU), rapid injection of a brain perfusion radiopharmaceutical at seizure onset followed by ictal SPECT imaging can provide the epilepsy surgical team with more specific localisation information to aid presurgical planning. In view of the potential benefits to epilepsy patients an Ictal SPECT service has been established in Beaumont Hospital. There are many challenges and complex issues to address when developing a routine Ictal SPECT service in order to provide a quality and safe service to patients and staff. A multi-disciplinary approach was taken when planning and developing this new service in Beaumont Hospital. Material(s) and Method(s): This procedure is carried out between the following departments: Nuclear Medicine Department, Neurology, the Epilepsy Monitoring Unit (EMU) and Neuro Physics. The following areas required careful development and planning for the project: (1) Patient Selection and Preparation: (2) Radiopharmaceutical Selection, Preparation and Dispensing: (3) Nuclear Medicine Radiation Protection Issues: (4) Patient monitoring and administration of Radiopharmaceutical on the EMU: (5) Nuclear Medicine Patient Scanning: (6) Data Post Processing (SISCOM): A site visit to UZ Leuven hospital Belgium occurred early in the project, this provided invaluable information and support from an experienced centre with a long established Ictal SPECT service. Result(s): There have been many unexpected challenges during the establishment of this service: - Supply issues of the Radiopharmaceutical tracer - The impact of Covid-19 - An issue with absorption of the radiopharmaceutical within the Delivery tubing system To date two patients have successfully undergone Ictal SPECT exams, both were administered the radiopharmaceutical within seconds of the onset of a seizure. The results of the Ictal SPECT exam were discussed at a multi-discipline meeting and were used in the patient pre-surgical planning. Conclusion(s): Ictal SPECT is an intricate procedure that requires extensive planning and co-operation between the multi-disciplinary team in order to provide a quality and safe service to the patient. Beaumont Hospital hopes to continue and expand this service.Copyright © 2023 Southern Society for Clinical Investigation.

Comparison of photographic photonic assessment and conventional clinical assessment in diagnosis of contact allergy with patch testing: a pilot study

The SARS-CoV-2 (COVID-19) pandemic has led to the rapid implementation of virtual clinics across the healthcare sector. Alternatives to the conventional face-to-face patient assessment have been sought and piloted within dermatology departments. Cutaneous patch testing is traditionally assessed on days 2 and 4, and often delayed readings are required. Strategies to minimize physical attendance and the potential risk of COVID-19 transmission were required in order to maintain access to services. Photographic assessment of patch testing was introduced in our department. In addition, we employed photographic phototonics to augment the patch-test result image. Phototonics is the technology of generating, detecting and manipulating physical light, whose quantum unit is the photon. Photonics can be used to assess levels of blood flow in a clinical photograph of skin acting as a surrogate marker for cutaneous inflammation. Our aim was to assess if clinical photography and photonic image analysis can improve the detection of positive reactions in the virtual interpretation of patchtest results. Consecutive patients attending for patch testing were recruited and written consent was obtained. Photographs of patch-test results were taken using a 40-megapixel colour camera, on day 5, contemporaneous to patch-test assessment by the study investigators. The photographs were then analysed using spectral imaging technology software (HyperCube). The analysis employed principal component analysis, a technique used to reduce the dimensionality of datasets. The phototonic images were then examined to determine a combination of variables or colour patterns (red-green-blue) that would indicate a positive result and a surrogate marker for cutaneous inflammation. Thirty patients were recruited from September to November 2020. Two blinded investigators determined whether the results were positive, ?positive, irritant or other. Phototonic, photographic and clinical results were then compared. Photonic evaluation captured 59% of positive patch-test readings, while photographic assessment captured 50%. Interpretation of the results was almost identical between both investigators. This pilot study outlines the potential application of phototonic technology in the interpretation of virtual patch-test results. It is evident that physical attendance for patch-test reading is superior to both photographic phototonic assessment and photographic assessment. However, there may be role for the use of phototonics in order to augment the evaluation of virtual patch-test results. Interpretation of phototonics can be difficult and is generally modelled to validated results. Analysis using a multispectral camera to include specific wavelengths to monitor increased blood flow may have a role.

mRNA expression and delivery efficacy of lipid nanoparticles in the cells breast tumor microenvironment: in vitro and in vivo evaluation

During the COVID-19 pandemics we have all witnessed the clinical importance of mRNA as current vaccines and future therapeutics. mRNA therapies have a potential to revolutionize cancer treatment. Delivery of mRNA requires lipid nanoparticles (LNP) to protect the cargo from degradation. mRNA has a negative charge and depends on positively charged lipids to be encapsulated in LNP. These lipids can be either ionizable at certain pH or constantly cationic. Even though previous studies had evaluated the formulation properties of ionizable and cationic LNP systems, there is the need to understand their specificity in terms of mRNA delivery and protein expression in breast cancer tumor microenvironment. The objective of this work was to assess the kinetics of LNP cellular uptake and mRNA expression inv breast cancer (BC) cells and fibroblasts, the most frequent cell type in the tumor microenvironment cells, while studying the mechanisms involved in differential behaviors of LNP formulated with cationic and ionizable lipids. To achieve this goal mRNA-LNP containing ionizable lipids (LNP-A) and cationic lipids (LNP-B) were designed and formulated using Nanoassemblr Benchtop microfluidics mixer (Precision NanoSystems). mRNA-LNP were characterized for size, zeta potential using dynamic light scattering (DLS) and mRNA encapsulation efficiency using RiboGreen assay. LNP were tagged with rhodamine lipid to investigate the uptake kinetic and a reporter GFP mRNA to evaluate mRNA expression in murine 4T1 and human MCF7, MDA-231, SUM-159 and T47D breast cancer cells and BJ fibroblasts. Live fluorescence microscopy imaging, IncuCyte S3, was used to determine the LNP uptake and GFP mRNA expression. In vitro biocompatibility was assessed with WST-1 assay. Additionally, expression of mRNA delivered from LNP in tumor microenvironment was evaluated in vivo in a syngeneic 4T1 breast cancer model using mRNA luciferase and IVIS imaging. mRNA-LNPs possessed an average diameter of 77 - 107 nm, narrow size distribution, neutral zeta potential and high mRNA encapsulation efficiency (>94%). Our results demonstrated that mRNA expression was higher in breast cancer cells when delivered from LNP-A formulation and in BJ fibroblasts when delivered from LNP-B. LNP-A, the ionizable LNP, was tested in the breast cancer cells to confirm the efficacy of the delivery. The highest transfection efficacy, from high to low, T-47D, MCF7, SUM-159, 4T1 and MDA-231.We have further investigated the cellular uptake mechanisms of LNP using uptake pathway inhibitors for caveolae endocytosis, clathrin endocytosis, and phagocytosis. Our data confirm that there are differences in mechanisms that govern the uptake of mRNA LNP in breast cancer cells and fibroblasts. Clathrin-mediated endocytosis was active in 4T1 breast cancer cells for ionizable and cationic LNP. Interestingly, despite in vitro differences in uptake and mRNA expression, in vivo results show that both formulations efficiently delivered luciferasemRNA in the tumor microenvironment. Histology results demonstrated similar luciferase expression for both LNP in tumors. Additionally, we were able to confirm the prominent presence of fibroblast and similar distribution in the 4T1 subcutaneous model which could explain the similar efficacy of cationic and ionizable LNP. Understanding uptake and mRNA expression of different LNP formulations in the tumor microenvironment can help in achieving the necessary protein expression for breast cancer therapies. Furthermore, determining the most efficient carrier in early stages may reduce the time required for clinical translation. Acknowledgement: This research was supported in part by CPRIT Core for RNA Therapeutics and Research.

Effect of Anticoagulants on Thromboembolic Events in Covid-19 Patients Discharged from Hospital and Outpatients

Background and Objective: The incidence of pulmonary thromboembolic disease (PTE) in COVID-19 patients has been reported from 14.8% up to 30% in various retrospective studies. The purpose of this study is to evaluate clinical and laboratory risk factors, as well as related medications such as anticoagulants, to predict the risk of thromboembolic disease and/or death in the COVID-19 patients. Method(s): Over a period of 14 months (August 2020 to September 2021), a total of 145 consecutive patients with signs and symptoms suspicious for pulmonary embolism (PE) were referred for perfusion single-photon emission computed tomography/computed tomography (Q SPECT/CT). All patients had a history of acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection diagnosed with a positive real-time polymerase chain reaction (RTPCR) test. Result(s): Among the 145 patients included in the study The risk of PE was found to be greater in elder patients (OR:1.05, p<0.001) (Odds Ratio [95% CI]: 1.05 [1.02-1.07], p<0.001) and in patients with higher maximum d-dimer levels (Odds Ratio [95% CI]: 1.14 [1.01-1.3], p=0.04). We also analyzed the utility of maximum d-dimer level for predicting acute PE with ROC curve analysis. For d-dimer = 0.5 mg/dL cut-off sensitivity is 91%, specificity is 23%, for d-dimer = 1 mg/dL cut-off sensitivity is 79%, specificity is 43% Conclusion(s): D-dimer titers were higher in the pulmonary embolism group in our study. Another significant finding was that anticoagulants did not prevent the development of pulmonary embolism in COVID-19 patients due to undergoing thromboinflamation possibly.

Characterization of respiratory sequelae following SARSCoV-2 infection, a monocenter study

Introduction: During the acute phase of SARS-CoV-2 infection, alveolar and microvascular damages are observed in some patients. These lesions are promoted by hyper inflammation and immunothrombosis, respectively. While dyspnea is a very prevalent symptom following SARS-CoV-2 infection, the consequences on the lung are currently poorly documented. Aims and objectives: We hypothesized that patients retained parenchymal and also vascular sequelae after the infection. This single-center ambispective study aimed to characterize these sequelae after the infection. Method(s): All patients hospitalized at the University Hospital of Caen for a PCR-proven SARS-CoV-2 infection were offered a follow-up including a clinical evaluation and the realization of complete LFT, non-injected CT scan, ventilation/perfusion single-photon emission computed tomography (SPECT), and a cardiopulmonary exercise testing (CET). This assessment was performed within 6 to 9 months after the infection. Result(s): 105 patients were included. At 6-9 months after infection, 71% of our patients retained radiological abnormalities, mainly ground glass and/or reticulations. LFT revealed that 21.3% of patients had abnormal FVC (<80%) and 51.2% of patients had abnormal DLCO (<80%). SPECT showed mismatched defects for 15% of patients. Finally, CET showed that 28.6% of the patients had an exercise limitation and 25% showed an abnormality of the vascular parameters. Conclusion(s): These preliminary data suggest the persistence of vascular and parenchymal abnormalities in a significant proportion of patients at 6-9 months after SARS-CoV-2 infection.

Macrophage membrane-biomimetic adhesive polycaprolactone nanocamptothecin for improving cancer-targeting efficiency and impairing metastasis

The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has stimulated intensive efforts to expand nanoparticle strategies to treat various diseases. Numerous synthetic nanoparticles have been developed for pharmaceutical delivery and cancer treatment. However, only a limited number of nanotherapies have enter clinical trials or are clinically approved. Systemically administered nanotherapies are likely to be sequestered by host mononuclear phagocyte system (MPS), resulting in suboptimal pharmacokinetics and insufficient drug concentrations in tumors. Bioinspired drug-delivery formulations have emerged as an alternative approach to evade the MPS and show potential to improve drug therapeutic efficacy. Here we developed a biodegradable polymer-conjugated camptothecin prodrug encapsulated in the plasma membrane of lipopolysaccharide-stimulated macrophages. Polymer conjugation revived the parent camptothecin agent (e.g., 7-ethyl-10-hydroxy-camptothecin), enabling lipid nanoparticle encapsulation. Furthermore, macrophage membrane cloaking transformed the nonadhesive lipid nanoparticles into bioadhesive nanocamptothecin, increasing the cellular uptake and tumor-tropic effects of this biomimetic therapy. When tested in a preclinical murine model of breast cancer, macrophage-camouflaged nanocamptothecin exhibited a higher level of tumor accumulation than uncoated nanoparticles. Furthermore, intravenous administration of the therapy effectively suppressed tumor growth and the metastatic burden without causing systematic toxicity. Our study describes a combinatorial strategy that uses polymeric prodrug design and cell membrane cloaking to achieve therapeutics with high efficacy and low toxicity. This approach might also be generally applicable to formulate other therapeutic candidates that are not compatible or miscible with biomimetic delivery carriers. © 2022 The Authors

Interaction of GC376, a SARS-COV-2 MPRO inhibitor, with model lipid membranes

Partitioning and effect of antiviral GC376, a potential SARS-CoV-2 inhibitor, on model lipid membranes was studied using dynamic light scattering (DLS), UV–VIS spectrometry, Excimer fluorescence, Differential scanning calorimetry (DSC) and Small- and Wide-angle X-ray scattering (SAXS/WAXS). Partition coefficient of GC376 between lipid and water phase was found to be low, reaching KP = 46.8 ± 18.2. Results suggest that GC376 partitions into lipid bilayers at the level of lipid head-groups, close to the polar/hydrophobic interface. Changes in structural and thermodynamic properties strongly depend on the GC376/lipid mole ratio. Already at lowest mole ratios GC376 induces increase of lateral pressures, mainly in the interfacial region of the bilayer. Hereby, the pre- and main-transition temperature of the lipid system increases, what is attributed to tighter packing of acyl chains induced by GC376. At GC376/DPPC ≥ 0.03 mol/mol we detected formation of domains with different GC376 content resulting in the lateral phase separation and changes in both, main transition temperature and enthalpy. The observed changes are attributed to the response of the system on the increased lateral stresses induced by partitioning of GC376. Obtained results are discussed in context of liposome-based drug delivery systems for GC376 and in context of indirect mechanism of virus replication inhibition.

Lung perfusion assessment in Long-COVID children: a pilot study

Aim/Introduction: There is growing interest in the clinical management of children with persisting and debilitating symptoms after Sars-COV-2 infection (Long-COVID). Chronic effects could arise from residual clot burden and small vessel inflammation, both expressing endothelial damage that may lead to lung perfusion impairment. 99mTc-macroaggregated albumin (MAA) SPECT/ CT is a well-established tool to detect lung perfusion defects, even at the small-vessels level. This pilot study aimed at assessing lung perfusion in Long-COVID children with MAA SPECT/CT and at comparing functional patterns with clinical scenarios during acute infection and follow-up. Material(s) and Method(s): Clinical and biochemical data were collected during acute infection and follow-up in 10 children (6 males and 4 females, mean age: 13.6 years) fulfilling Long-COVID diagnostic criteria and complaining of chronic fatigue and post-exertional malaise after mild efforts. All patients underwent a cardiopulmonary test and MAA SPECT/CT scan. Dose activities were properly chosen according to the EANM guidelines for lung scintigraphy in children. Intravenous injections were administered to patients in the supine position immediately before the planar scan, which was followed by the lung SPECT/CT acquisition. Reconstructed studies were visually analyzed. Imaging results were compared with clinical scenarios during acute infection and follow-up. Result(s): The severity of acute disease was mild and moderate in 6/10 (60 %) and 2/10 (20 %) children, respectively;there were no significant symptoms in the remaining 2 cases. Persisting symptoms after the acute phase were observed in 7/10 (70%) patients. Five out of 10 (50.0%) children showed perfusion defects on MAA SPECT/CT scan, without morphological alterations on co-registered CT. In particular, 4/5 (80%) children with lung perfusion abnormalities were previously affected by a mild acute infection, whereas a single child (20%) was asymptomatic. However, during the follow-up, persisting symptoms (e.g., headache and dyspnea after the cardiopulmonary test) were detected in 5/5 (100%) patients. Conversely, among the five children without lung perfusion defects, only 2 (40%) showed persisting symptoms (in particular, headache), while 3 (60%) children had dyspnea after the cardiopulmonary test. Conclusion(s): This pilot study showed lung perfusion defects in Long-COVID children. Despite the small patient sample, perfusion abnormalities on MAA SPECT/CT seem to occur more frequently in children with persisting symptoms following the acute infection and dyspnea after the cardiopulmonary test. Larger cohort studies are needed to confirm these preliminary results, providing a better selection among children who can benefit the most from MAA SPECT/CT imaging.

Disparities in pediatric patients receiving proton therapy during the COVID-19 pandemic - A single institutional experience

Introduction: Our institution cares for a largely underserved urban population, treating about 120 children annually with radiation therapy;roughly 10% are referred for proton therapy elsewhere. COVID-19 led to some decreases in medical care due to uncertainties regarding the state of public health. The purpose of this study is to evaluate existing socioeconomic disparities using the University of Wisconsin Area Deprivation Index (ADI) and whether the pandemic impacted this referral pattern. Method(s): Over the last twenty years, approximately 2,275 children have presented to our institution for radiation treatment. A retrospective chart review was conducted and a patient database of demographic and clinical information was created. We used demographic data to obtain the ADI, and compared relative disparity rankings between proton therapy recipients and a random sample of patients from the 25 most common zip codes (representative of over 20% of the total cohort). We compared the number of patients treated only at the closest proton facility before and after the onset of the pandemic. Result(s): The demographic make-up of our patient population is approximately 53.7% Latino, 22.6% White, 9.5% African American, 9.2% Asian, and 5% Other. Of these patients, about 500 had diagnoses typically referred for proton therapy (such as brain tumors, neuroblastoma, sarcomas, and Hodgkin lymphoma). At baseline, we found a statistically significant difference in the median state ADI decile of 3 and 7 for protons and photons, respectively, reflecting lower socioeconomic disadvantage in the proton group. There was a difference in the median household income (based on zip code) of $102,028 and $70,479 between the proton and photon groups (p < 0.0001). There was also a difference in median household income of $57,871 and $76,808 between Latino and Non-Latino patients (p < 0.0001). Demographic data for the proton therapy cohort showed that 46.2% of these patients were White, 15.4% were Latino, 15.4% were African American, 7.7% were Asian, and 15.4% were Other. At the closest proton facility, between 2014-2019, 16 of our patients received radiation therapy. Since the beginning of pandemic associated restrictions in March 2020, 19 patients have received proton therapy at this center. Conclusion(s): Disparities preventing patients from receiving proton therapy have been described. Our work adds granular census block data and uses the ADI which takes into account median family income, unemployment rate, households without access to a vehicle, English language proficiency and more. Those with lower ADI risk rankings were overrepresented in the proton therapy group. Despite the pandemic and added referral challenges, the number of patients able to receive proton therapy did not decrease which we hypothesize may be due to many factors, including the unanticipated flexibility of remote work amongst those with lower ADI rankings. Latinos were least likely to have proton therapy, and further research is needed to ameliorate the disparities and barriers to care which they face.

Lung Ventilation and Perfusion SPECT in long-COVID-19

Aim/Introduction: Knowledge about COVID-19's physiopathology is still scarce, mainly with respect to the recovery phase. Nonetheless, its association with an increased incidence of thromboembolic phenomena is well established. Ventilation/Perfusion single-photon emission computed tomography (VP-SPECT) plays a major role in the evaluation of pulmonary embolism (PE) and microvascular disease, given its high sensibility and low radiation burden. We aim, with this study, to review the contribution of VP-SPECT in these patients' follow-up, with a particular focus on those with long-COVID-19. Material(s) and Method(s): We performed a retrospective study with COVID-19 patients that underwent VP-SPECT in our Department, until march-2022. Functional impairment of global pulmonary perfusion (FIGPP) was quantified by assigning points for each segment with a mismatch defect (a total of 36 points in 18 segments). PE was defined by the presence of segmental or subsegmental pleural-based mismatch defect(s) assessed at least 2 points. All relevant demographic/clinical data were collected. Result(s): Sixty patients (mean age 54.8+/-12.8 years, 51.3% female) with a history of COVID-19 underwent VP-SPECT on average 285.6+/-127.2 days after infection. There was a high prevalence of severe infections (58%, N=29) and admitted patients (64.9%, N=37), with a mean length of stay in the hospital of 22.5+/-17.2 days. Six patients (10.2%) had acute PE associated. The main reason for VPSPECT was post-infection fatigue/dyspnoea (71.7%;N=43). Only 6.9% of patients underwent VP-SPECT during acute disease (N=4). Median FIGPP was 6% (0-47). Patients who were hospitalized (p=0.066) or who had severe disease (p=0.161) showed no statistically significant differences in FIGPP. Management change after VP-SPECT occurred in 11.9% (N=7). Patients who did not start anticoagulant therapy (N=46) showed a median FIGPP of 6% (0-18). Conclusion(s): Our findings suggest that, although clinically relevant, persistent post-COVID-19 fatigue/dyspnoea symptoms do not appear to be justified by a FIGPP associated with significant thromboembolism and are unrelated to disease severity and need for hospitalisation. However, VP-SPECT played an important role both in excluding serious sequelae of thromboembolism and in identifying patients at higher risk of developing pulmonary hypertension.

Lung VQ scan in COVID-19: Various patterns of perfusion defects

Aim/Introduction: While COVID-19 infection is associated with the increased risk of pulmonary thromboembolism (PTE), it may also affects the lungs that causes ventilation-perfusion (VQ) patterns other than PTE. Although extensive research has been done to address different anatomical patterns of COVID-19, there is a knowledge gap in terms of VQ lung scintigraphy in these patients. The purpose of this study is to demonstrate these patterns and to show how important it is to use SPECT/CT in addition to planar images to differ these patterns from PTE [1, 2, 3]. Material(s) and Method(s): We collected lung scans performed in 64 patients with history of past/recent COVID-19 infection (in the preceding 1.5 years) who were referred for VQ scintigraphy. The scan was performed using Q-SPECT/Q-planar (26.6%), Q-SPECT/CT (42.2%), VQ-SPECT (14%) and VQ-SPECT/CT (17.2%). Interpretation was based on the EANM criteria. Result(s): Of these patients 10 (15.6%) had positive scan for PTE. Moreover, in 49 (76.6%) of these patients, anatomical abnormalities were observed compatible with COVID-19 infection. The patterns seen were as follows: 1) apparent hot spot due to focal sparing of lung, 2) zones of decreased and increased perfusion, 3) zones of normal and increased perfusion, 4) small sub-segmental defects matching with CT findings, and 5) reverse mismatched defects. Also, a case of loculated pleural effusion in CT with Q abnormalities was observed. Conclusion(s): Lung perfusion abnormalities are common findings in COVID-19 patients. They are usually either due to pulmonary embolism, parenchymal infiltrates, or other causes of mosaic attenuation related to, but not specific of the pathophysiology of COVID-19 infection. The value of VQ SPECT/CT imaging to detect and differentiate the various types of Q abnormalities was noticeable.

Why Technegas is Fast Replacing 99mTc-Based Aerosols in Lung Scintigraphy

Aim/Introduction: Technegas is fast becoming the gold standard for lung ventilation scintigraphy in Canada. Technegas is a carbonbased nanoparticle bound to 99mTc which is small enough to behave more like a gas than an aerosol. Due to its small size, Technegas can easily perfuse the peripheral airways and does not aggregate in the central airways like larger aerosol particles often do. Furthermore, since the Covid-19 pandemic began, there has been a significant drop in ventilation studies performed due to the risk of exposure to the virus when using traditional aerosols. Improved image quality, fast and easy administration, enhanced patient comfort, and ability to safely administer Technegas with Covid-19 positive patients makes Technegas far superior to traditional Tc-based aerosols. Material(s) and Method(s): A review of the literature comparing Technegas to other commonly used 99mTcbased lung ventilation imaging agents was conducted. Recent purchasers of Technegas units were interviewed to determine their motivation for switching to Technegas and their overall impression with using it after changing over. Result(s): The small particle size, reduced central airways deposition, and lack of lung clearance leads to improved count-statistics and better target-to-non-target ratio, which allows for SPECT imaging, which is not feasible when using traditional aerosols. Technologists report that administering Technegas is far easier and faster than administering traditional aerosols. Often patients only require 1 or 2 breaths of Technegas to achieve the desired count rate, as opposed to 5 or more minutes of breathing an aerosol. Technegas is a 'dry' aerosol, which means that it is considered a non-aerosol generating procedure, so it is safe to use on Covid-19 positive patients. Justifying the small start-up cost to purchase a Technegas generator was the limiting factor for departments delaying their switch to Technegas. Canada's health care system is publicly-funded, which often delays widespread access to technological advancements. The Covid-19 pandemic has increased demand for Technegas across Canada, which has resulted in increased funding to purchase more Generators. Conclusion(s): Technegas is far superior to other 99mTc-based aerosols used in ventilation imaging and is fast replacing Tc-based aerosols as the agent of choice in nuclear medicine departments across Canada.

Nanosized graphite encapsulating technetium-99m metal complexes for lung ventilation studies in rats

Aim/Introduction: Many diseases with high prevalence and socioeconomic impact are caused by, or associated with, altered lung ventilation patterns. These include chronic obstructive pulmonary disease, COVID-19 infection, asthma, or lung cancer. SPECT/ CT images using a dispersion of nanosized (30-60nm) graphite encapsulating technetium-99m metal NG-eTcM (such as Technegas) are widely used to assess regional lung ventilation in the clinical setting. However, evaluation of lung ventilation in experimental animals has been barely explored. The main objective of this study was to develop and construct a system to deliver NG-eTcM to rats and obtain high resolution microSPECT/CT images of the lungs after administration of the radiotracer. Material(s) and Method(s): To adapt the human administration system for rats, a special chamber was designed, in which NG-eTcM was delivered from the NG-eTcM generator. The chamber was designed with pressure gauges, inlet and outlet checkvalves, a vacuum system to simulate deep inhalation and 3D-printend nozzles to place up to two anesthetised rats with their snouts into the chamber to inhale the technetiumgraphite suspension. NG-eTcM was prepared according to the manufacturer instructions (370 MBq in 0,1 mL) from a fresh eluate of a 99Mo/99mTc generator. Anesthetized Wistar rats were placed with the snout into the inhalation chamber for 10 minutes and images were obtained 12 and 50min post-administration in a U-SPECT6/Eclass microSPECT/CT scanner. SPECT images were reconstructed and attenuation correction applied using the CT attenuation map. SPECT/CT images were qualitatively analysed and compared with previously obtained microPET/CT images from our group using [18F] SF6 (1). Result(s): The designed system was shown to be amenable for NG-eTcM administration to rats. MicroSPECT/CT images were properly acquired, and they showed the radiopharmaceutical was able to reach the lungs. The system can easily be modified for studies in mice. When compared to microPET/CT images with [18F] SF6, the distribution pattern is much less homogeneous, probably due to the different nature of NG-eTcM nanoparticle suspension, not optimized for animal use, vs. a pure gas. Conclusion(s): The commercially available administration system of TechnegasTM has been modified for its use in preclinical studies. NG-eTcM can properly be delivered to rats by inhalation, allowing MicroSPECT/ CT studies in animal models of diseases producing altered lung ventilation patterns.

Lung VQ scan in COVID-19: Various patterns of perfusion defects

Aim/Introduction: While COVID-19 infection is associated with the increased risk of pulmonary thromboembolism (PTE), it may also affects the lungs that causes ventilation-perfusion (VQ) patterns other than PTE. Although extensive research has been done to address different anatomical patterns of COVID-19, there is a knowledge gap in terms of VQ lung scintigraphy in these patients. The purpose of this study is to demonstrate these patterns and to show how important it is to use SPECT/CT in addition to planar images to differ these patterns from PTE [1, 2, 3]. Material(s) and Method(s): We collected lung scans performed in 64 patients with history of past/recent COVID-19 infection (in the preceding 1.5 years) who were referred for VQ scintigraphy. The scan was performed using Q-SPECT/Q-planar (26.6%), Q-SPECT/CT (42.2%), VQ-SPECT (14%) and VQ-SPECT/CT (17.2%). Interpretation was based on the EANM criteria. Result(s): Of these patients 10 (15.6%) had positive scan for PTE. Moreover, in 49 (76.6%) of these patients, anatomical abnormalities were observed compatible with COVID-19 infection. The patterns seen were as follows: 1) apparent hot spot due to focal sparing of lung, 2) zones of decreased and increased perfusion, 3) zones of normal and increased perfusion, 4) small sub-segmental defects matching with CT findings, and 5) reverse mismatched defects. Also, a case of loculated pleural effusion in CT with Q abnormalities was observed. Conclusion(s): Lung perfusion abnormalities are common findings in COVID-19 patients. They are usually either due to pulmonary embolism, parenchymal infiltrates, or other causes of mosaic attenuation related to, but not specific of the pathophysiology of COVID-19 infection. The value of VQ SPECT/CT imaging to detect and differentiate the various types of Q abnormalities was noticeable.

The Luminescence Hypothesis of Olfaction.

A new hypothesis for the mechanism of olfaction is presented. It begins with an odorant molecule binding to an olfactory receptor. This is followed by the quantum biology event of inelastic electron tunneling as has been suggested with both the vibration and swipe card theories. It is novel in that it is not concerned with the possible effects of the tunneled electrons as has been discussed with the previous theories. Instead, the high energy state of the odorant molecule in the receptor following inelastic electron tunneling is considered. The hypothesis is that, as the high energy state decays, there is fluorescence luminescence with radiative emission of multiple photons. These photons pass through the supporting sustentacular cells and activate a set of olfactory neurons in near-simultaneous timing, which provides the temporal basis for the brain to interpret the required complex combinatorial coding as an odor. The Luminescence Hypothesis of Olfaction is the first to present the necessity of or mechanism for a 1:3 correspondence of odorant molecule to olfactory nerve activations. The mechanism provides for a consistent and reproducible time-based activation of sets of olfactory nerves correlated to an odor. The hypothesis has a biological precedent: an energy feasibility assessment is included, explaining the anosmia seen with COVID-19, and can be confirmed with existing laboratory techniques.